Abstract
The prolongation of life and the rapidly increasing incidence of Alzheimer’s disease have brought to the foreground the need for greater understanding of the etiology of the disease and the means to prevent or at least slow down the process. Out of this need the transgenic mouse and the production of synthetic amyloid peptides have been developed in an attempt to create experimental models of Alzheimer’s disease that will help our understanding of the cellular and molecular mechanisms by which the pathology leads to memory dysfunction and to test potential therapeutic strategies. Despite 10 or so years of reasonably intensive research with these models, both fall short of producing a viable and faithful model of the complete pathology of Alzheimer’s disease and the behavioral consequences are far from modelling the progressive decline in cognitive function. Here we review the advantages and the caveats associated with the two models in terms of the pathology, the associated memory dysfunction, and the effect on synaptic plasticity. Given the more recent advances that have been made in the understanding of the neurobiological changes that occur with the disease and with the consideration of other environmental effects, which have been clearly shown to have an impact on the progression of the disease in humans, we emphasis the advantage of pharmacological or environmental in transgenic mice or rodents injected with synthetic peptides that may prove to be more fruitful in our understanding of the memory deficits associated with the disease.
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Arendash G. W., King D. L., Gordon M. N., Morgan D., Hatcher J. M., Hope C. E., and Diamond D. M. (2001) Progressive, age-related behavioural impairments in transgenic mice carrying both mutant amyloid precursor protein and presenilin-1 transgenes. Brain Res. 891, 42–53.
Arendt T. (2001a) Disturbance of neuronal plasticity is a critical pathogenetic event in Alzheimer’s disease. Int. J. Devl. Neurosci. 19, 231–245.
Arendt T. (2001b) Alzheimer’s disease as a disorder of mechanisms underlying structural brain self organisation. Neuroscience 4, 723–765.
Arriagada P. V., Growdon J. H., Hedley-White E. T., and Hyman B. T. (1992) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease. Neurology 42, 631–639.
Bales K. R., Verina T., Cummins D. J., et al. (1999) Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 96, 15,233–15,238.
Barrow C. J. and Zagorski M. G. (1991) Solution structures of beta peptide and its constituent fragments: relation to amyloid deposition. Science 253, 179–182.
Bartoo G. T., Nochlin D., Chang D., Kim Y., and Sumi S. M. (1997) The mean Aβ load in the hippocampus correlates with duration and severity of dementia in subgroups of Alzheimer disease. J. Neuropathol. Exp. Neurol. 56, 531–540.
Behl C., Davies J. B., Lesley R., and Schubert D. (1994) Hydrogen peroxide mediates amyloid β protein toxicity. Cell 77, 817–827.
Benzi G. and Moretti A. (1995) Are reactive oxygen species involved in Alzheimer’s disease? Neurobiol. Aging 16, 661–674.
Berg L., McKeel Jr. D. W., Millar J. P., Baty J., and Morris J. C. (1993) Neuropathological indexes of Alzheimer’s disease in demented and nondemented persons aged 80 years and older. Arch. Neurol. 50, 349–358.
Borchelt D. R., Thinakaran G., Eckman C. B., et al. (1996) Familial Alzheimer’s disease-linked presenilin 1 variants elevate Abeta1–42/1–40 ratio in vitro and in vivo. Neuron 17, 1005–1013.
Borchelt D. R., Ratovistsky T., van Lare J., Lee M. K., et al. (1997) Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins? Neuron 19, 939–945.
Bornemann K. D., Wiederhold K. H., Pauli C., et al. (2001) Abeta-induced inflammatory processes in microglia cells of APP23 transgenic mice. Am. J. Pathol. 158, 63–73.
Braak H. and Braak E. (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 82, 239–259.
Breitner J. C. S., Welsh K. A., Helms M. J., et al. (1995) Delayed onset of Alzheimer’s disease with non steriodian anti inflammatory and histamine H2 blocking drugs. Neurobiol. Aging 16, 523–530.
Bruce A. J., Malfroy B., and Baudry M. (1996) β-Amyloid toxicity in organotypic hippocampal cultures: protection by EUK-8, a synthetic catalytic free radical scavenger. Proc. Natl. Acad. Sci. USA 93, 2312–2316.
Bush A. I., Multhaup G., Moir R. D., et al. (1993) A novel zinc (II) binding site modulates the function of the beta A4 amyloid protein precursor of Alzheimer’s disease. J. Biol. Chem. 268, 16,190–16,112.
Calhoun M. E., Wiederhold K. H., Abramowski D., et al. (1998) Neuron loss in APP transgenic mice. Nature 395, 755–756.
Campion D., Flaman J. M., Brice A., et al. (1995) Mutations of the presenilin 1 gene in families with early-onset Alzheimer’s disease. Hum. Mol. Genet. 4, 2372–2377.
Carter D. B., Dunn E., McKinley D. D., et al. (2001) Human apolipoprotein E4 accelerates beta-amyloid deposition in APPsw transgenic mouse brain. Ann. Neurol. 50, 468–475.
Castegna A., Aksenov M., Aksenova M., et al. (2002) Proteomic identification of oxidatively modified proteins in Alzheimer’s disease brain. part 1: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. Free Radic. Biol. Med. 33, 562–571.
Chapman P. F., White G. L., Jones M. W., et al. (1999) Impaired synaptic plasticity and learning aged amyloid precursor protein transgenic mice. Nature Neurosci. 2, 271–276.
Check E. (2002) Nerve inflammation halts trials for Alzheimer’s drug. Nature 415, 462.
Chen G., Chen K. S., Knox J., et al. (2000) A learning deficit related to age and β-amyloid plaques in a mouse model of Alzheimer’s disease. Nature 408, 975–982.
Chen S. Y., Wright J. W., and Barnes C. D. (1996) The neurochemical and behavioural effects of beta-amyloid peptide (25–35). Brain Res. 720, 54–60.
Chishti M. A., Yand D-S, Janus C., Phinney A. L., et al. (2001) Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. J. Biol. Chem. 276, 21,562–21,570.
Chui D. H., Tanahashi H., Ozawa K., et al. (1999) Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation. Nature Med. 5, 560–564.
Citron M., Westaway D., Xia W., et al. (1997) Mutant presenilins of Alzheimer’s disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice. Nature Med. 3, 67–72.
Citron M., Eckman C. B., Diehl T. S., et al. (1998) Additive effects of PS1 and APP mutations on secretion of the 42-residue amyloid beta-protein. Neurobiol Dis. 5, 107–116.
Cleary J., Hittner J. M., Semotuk M., Mantyh P., and O’Hare E. (1995) Beta-amyloid(1–40) effects on behavior and memory. Brain Res. 682, 69–74.
Combs C. K., Johnson D. E., Cannady S. B., Lehman T. M., and Landreth G. E. (1999) Identification of microglial signal transduction pathways mediating a neurotoxic response to amyloidogenic fragments of β-amyloid and prion proteins. J. Neurosci. 19, 928–939.
Cotman C. W., Pike C. J., and Copani A. (1992) beta-Amyloid neurotoxicity: a discussion of in vitro findings. Neurobiol. Aging 13, 587–590.
Cruts M., Hendriks L., and Van Broeckhoven C. (1996) The presenilin genes: a new gene family involved in Alzheimer’s disease pathology. Hum. Mol. Genet. 5, 1449–1455.
Cummings B. J., Pike C. J., Shankle R., and Cotman C. W. (1996) Beta-amyloid deposition and other measures of neuropathology predict cognitive status in Alzheimer’s disease. Neurobiol. Aging 17, 921–933.
Czech C., Tremp G., and Pradier L. (2000) Presenilins and Alzheimer’s disease: biological functions and pathogenic mechanisms. Progs. Neurobiol. 60, 363–384.
Delobette S., Privat A., and Maurice T. (1997) In vitro aggregation facilitates beta-amyloid peptide-(25–35)-induced amnesia in the rat. Eur. J. Pharmacol. 319, 1–4.
DeStrooper B., Saftig P., Craessaerts K., et al. (1998) Deficiency of presenilin 1 inhibits the normal cleavage of amyloid precursor protein. Nature 391, 387–390.
Davies C. A., Mann D. M., Sumpter P. Q., And Yates P. O. (1987) A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer’s disease. J. Neurol. Sci. 78, 151–164.
Dewachter I., Van Dorpe J., Smeijers L., et al. (2000) Aging increased amyloid peptide and caused amyloid plaques in brain of old APP/V7171 transgenic mice by a different mechanism than mutant Presenilin1. J. Neurosci. 20, 6452–6458.
Dickson D. W. (1997) The pathogenesis of senile plaques. J. Neuropath. Exp. Neurol. 56, 321–339.
Dineley K. T., Westerman M., Bui D., Bell K., Ashe K. H., and Sweatt J. D. (2001) β-Amyloid activates the mitogen-activated protein kinase cascade via hippocampal α7 nicotinic acetylcholine receptors: in vitro and in vivo mechanisms related to Alzheimer’s disease. J. Neurosci. 21, 4125–4133.
Dodart J. C., Meziane H., Mathis C., Bales K. R., Paul S. M., and Ungerer A. (1999) Behavioral disturbances in transgenic mice overexpressing the V717F beta-amyloid precursor protein. Behav. Neurosci. 113, 982–990.
Dodart J. C., Mathis C., Saura J., Bales K. R., Paul S. M., and Ungerer A. (2000) Neuroanatomical abnormalities in behaviorally characterized APP(V717F) transgenic mice. Neurobiol. Dis. 7, 71–85.
Dornan W. A., Kang D. E., McCampbell A., and Kang E. E. (1993) Bilateral injections of beta A(25–35) + IBO into the hippocampus disrupts acquisition of spatial learning in the rat. Neuroreport 5, 165–168.
Duff K., Eckman C., Zehr C., et al. (1996) Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature 383, 710–713.
Duff K., Knight H., Refolo L. M., et al. (2000) Characterization of pathology in transgenic mice over-expressing human genomic and cDNA tau transgenes. Neurobiol. Dis. 7, 87–98.
Dumery L., Bourdel F., Soussan Y., Fialkowsky A., Viale S., Nicolas P., and Reboud-Ravaux M. (2001) β-amyloid protein aggregation: its implication in the physiopathology of Alzheimer’s disease. Path. Biol. 49, 72–85.
El Khoury J., Hickman S. E., Thomas C. A., Cao L., Silverstein S. C., and Loike J. D. (1996) Scavenger receptor-mediated adhesion of microglia to β-amyloid fibrils. Nature 382, 716–719.
Estus S., Tucker H. M., van Rooyen C., Wright S., Brigham E. F., Wogulis M., and Rydel R. E. (1997) Aggregated amyloid-beta protein induces cortical neuronal apoptosis and concomitant “apoptotic” pattern of gene induction. J. Neurosci. 17, 7736–7745.
Farrar L., Cupples L. A., van Duijn C. M., et al. (1995) Apolipoprotein E genotype in patients with Alzheimer’s disease: implications for risk of dementia among relatives. Ann. Neurol. 38, 797–808.
Fitzjohn S. M., Morton R. A., Keunzi F., et al. (2001) Age-related impairment of synaptic transmission but normal long-term potentiation in transgenic mice that overexpress the human APP695SWE mutant form of amyloid precursor protein. J. Neurosci. 21, 4691–4698.
Folstein M. F. and Whitehouse P. J. (1983) Cognitive impairment of Alzheimer disease. Neurobehav. Toxicol. Teratol. 5, 631–634.
Frautschy S. A., Hu W., Kim P., Miller S. A., Chu T., Harris-White M. E., and Cole G. M. (2001) Phenolic anti-inflammatory antioxidant reversal of Aβ-induced cognitive deficits and neuropathology. Neurobiol. Aging 22, 993–1005.
Friedlich A. L. and Butcher L. L. (1994) Involvement of free oxygen radicals in β-amyloidosis: an hypothesis. Neurobiol. Aging 15, 443–455.
Fukuchi K., Kamino K., Deeb S. S., Smith A. C., Dang T., and Martin G. M. (1992) Overexpression of amyloid precursor protein alters its normal processing and is associated with neurotoxicity. Biochem. Biophys. Res. Comm. 182, 165–173.
Gahtan E. and Overmier J. B. (1999) Inflammatory pathogenesis in Alzheimer’s disease: biological mechanisms and cognitive sequeli. Neurosci. Biobehav. Rev. 23, 615–633.
Games D., Adams D., Alessandrini R., et al. (1995) Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature 373, 523–527.
Giovannelli L., Casamenti F., Scali C., Bartolini L., and Pepeu G. (1995) Differential effects of amyloid peptides beta-(1–40) and beta-(25–35) injections into the rat nucleus basalis. Neuroscience 66, 781–792.
Giulian D. (1999) Microglia and the immune pathology of Alzheimer disease. Am. J. Hum. Genet. 65, 13–18.
Goate A., Chartier H. M., Mullan M., et al. (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349, 704–706.
Goedert M. J., Strittmatter J., and Roses A. D. (1994) Risky apolipoprotein in brain. Nature 372, 45–46.
Gomez-Isla T., Hollister R., West H., et al. (1997) Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer’s disease. Ann. Neurol. 41, 17–24.
Gordon M. N., King D. L., Diamond D. M., et al. (2001) Correlation between cognitive deficits and Aß deposits in transgenic APP+PS1 mice. Neurobiol. Aging 22, 377–386.
Gordon M. N., Holcomb L. A., Jantzen P. T., et al. (2002) Time course of the development of Alzheimer-like pathology in the doubly transgenic PS1 + APP mouse. Exp. Neurol. 173, 183–195.
Gotz J., Chen F., Barmettler R., and Nitsch R. M. (2001) Tau filament formation in transgenic mice expressing P301L tau. J. Biol. Chem. 276, 529–534.
Greenberg B. D., Ali S. M., Howland D., et al. (1993) Transgenic mouse studies of Alzheimer amyloid precursor. In Amyloid and Amyloidosis (Kisilevsky R., Benson E. D., Frangioni B., Gauldie J., Muckle T. J., and Young I. D., eds.), Parthenon publishing, New York, pp. 328–331.
Greenberg B. D. (1995) The COOH-terminus of the Alzheimer amyloid Aβ peptides: Differences in length influences the process of amyloid deposition in Alzheimer brain, and tell us something about relationships among parenchymal and vessel-associated amyloid deposits. Amyloid: Int. J. Exp. Clin. Invest. 2, 195–203.
Griffin W.S.T., Sheng J. G., and Mrak R. E. (1997) Inflammatory pathways. Implications in Alzheimer’s disease. In Molecular Mechanisms of Dementia (Wasco W. and Tanzi R. E., eds) Humana, Totowa, NJ, pp. 169–176.
Grundke-Iqbal I., Iqbal K., Quinlan M., Tung Y. C., Zaidi M. S., and Wisniewski H. M. (1986a) Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J. Biol. Chem. 261, 6084–6089.
Grundke-Iqbal I., Iqbal K., Tung Y. C., Quinlan M., Wisniewski H. M., and Binder L. I. (1986b) Abnormal phosphorylation of the microtubule-associated protein tau in Alzheimer cytoskeletal pathology. Proc. Natl. Acad. Sci. USA 83, 4913–4917.
Guénette S. Y. and Tanzi R. E. (1999) Progress toward valid transgenic mouse model for Alzheimer’s disease. Neurobiol. Aging 20, 201–211.
Halliwell B. (1992) Oxygen radicals as key mediators in neurological disease: fact or fiction? Ann. Neurol. 32, S10-S15.
Harris M. E., Hensley K., Butterfield D. A., Leedle R. A., and Carney J. M. (1995) Direct evidence of oxidative injury produced by the Alzheimer’s beta-amyloid peptide (1–40) in cultured hippocampal neurons. Expl. Neurol. 131, 193–202.
Hartley D. M., Walsh D. M., Ye C. P., Diehl T., Vasquez S., Vassilev P. M., Teplow D. B., and Selkoe D. J. (1999) Protofibrillar intermediates of amyloid β-protein induces acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J. Neurosci. 19, 8876–8884.
Hensley K., Carney J. M., Mattson M. P., Aksenova M., Harris M., Wu J. F., Floyd R. A., and Butter-field D. A. (1994) A model for β-amyloid aggregation and neurotoxicity based on free-radical generation by the peptide: relevance to Alzheimer disease. Proc. Natl. Acad. Sci. USA 91, 3270–3274.
Hesse L., Behr D., Masters C. L., and Multhaup G. (1994) The beta A4 amyloid precursor protein binding to copper. FEBS Lett. 349, 109–116.
Higgins L. S., Catalano R., Quon D., and Cordell B. (1993) Transgenic mice expressing human β-APP751 but not mice expressing β-APP695 display early Alzheimer’s disease-like histopathology. Ann. NY Acad. Sci. 695, 224–227.
Higgins L. S., Rodems J. M., Catalano R., Quon T., and Cordell B. (1995) Early Alzheimer disease-like histopathology increase in frequency with age in mice transgenic for β-APP751. Proc. Natl. Acad. Sci. USA 92, 4402–4406.
Holcomb L., Gordon M. N., McGowan E., et al. (1998) Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nature Med. 4, 97–100.
Holcomb L. A., Gordon M. N., Jantzen P., Hsiao K., Duff K., and Morgan D. (1999) Behavioral changes in transgenic mice expressing both amyloid precursor protein and presenilin-1 mutations: lack of association with amyloid deposits. Behav Genet. 29, 177–185.
Horsburgh K., McCarron M. O., White F., and Nicoll J. A. (2000) The role of apolipoprotein E in Alzheimer’s disease, acute brain injury and cerebrovascular disease: evidence of common mechanisms and utility of animal models. Neurobiol. Aging 21, 245–255.
Hsia A. Y., Masliah E., McConlogue L., et al. (1999) Plaque-independent disruption of neural circuits in Alzheimer’s disease mouse models. Proc. Natl. Acad. Sci. USA 96, 3228–3233.
Hsiao K., Chapman P., Nilsen S., Eckman C., Harigaya Y., Younkin S., Yang F., and Cole G. (1996) Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 274, 99–102.
Hughes C. P., Berg L., Danziger W. L., Coben L. A., and Martin R. L. (1982) A new clinical scale for the staging of dementia. Br. J. Psychiat. 140, 566–572.
Irizarry M., McNamara M., Fedorchak K., Hsiao K., and Hyman B. (1997a) APPsw transgenic mice develop age-related Aβ deposits and neuropil abnormalities, but no neuronal loss in CA1. J. Neuropathol. Exp. Neurol. 56, 965–973.
Irizarry M. C., Soriano F., McNamara M., Page K. J., Schenk D., Games D., and Hyman B. T. (1997b) Aβ deposition is associated with neuropil changes, but not with overt cell loss in the PDAPP transgenic mice. J. Neurosci. 17, 7053–7059.
Ishihara T., Hong M., Zhang B., Nakagawa Y., Lee M. K., Trojanowski J. Q., and Lee V. M. (1999) Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron 24, 751–762.
Ishihara T., Zhang B., Higuchi M., Yoshiyama Y., Trojanowski J. Q., and Lee V. M. (2001) Agedependent induction of congophilic neurofibrillary tau inclusions in tau transgenic mice. Am. J. Pathol. 158, 555–562.
Iwatsubo T. (1998) Aβ42, presenilins and Alzheimer’s disease. Neurobiol. Aging 19, 11–13.
Janus C., Pearson J., McLaurin J., et al. (2000a) Aβ peptide immunisation reduces behavioural impairement and plaques in a model of Alzheimer’s disease. Nature 408, 979–982.
Janus C., D’Amelio S., Amitay O., et al. (2000b) Spatial learning in transgenic mice expressing human presenilin 1 (PS1) transgenes. Neurobiol. Aging 21, 541–549.
Jarrett J. T. and Landsbury P. T. (1993) Seeding “one-dimensional crystallisation” of amyloid: a pathogenic mechanism of Alzheimer’s disease and Scrapie? Cell 73, 1055–1058.
Jin L. W., Ninomiya H., Roch J. M., Schubert D., Masliah E., Otero D. A., and Saitoh R. (1994) Peptides containing the RERMS sequence of amyloid beta/A4 protein precursor bind cell surface and promote neurite extension. J. Neurosci. 14, 5461–5470.
Johnson S. A., Rogers J., and Finch C E. (1989) APP-695 transcript prevalence is selectively reduced during Alzheimer’s disease in cortex and hippocampus but not in cerebellum. Neurobiol. Aging 10, 755–760.
Johnson S. A., McNeill T., Cordell B., and Finch C. E. (1990) Relation of neuronal APP-751/APP-695 mRNA ratio and neuritic plaque density in Alzheimer’s disease. Science 248, 854–857.
Johnson-Wood K., Lee M., Motter R., et al. (1997) Amyloid precursor protein processing and Aβ42 deposition in a transgenic mouse model of Alzheimer disease. Proc. Natl. Acad. Sci. USA 94, 1550–1555.
Jones M. W., Errington M. L., French P. J., et al. (2001) A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories. Nature Neurosci. 4, 289–296.
Kalback W., Watson M. D., Fitzjohn T. A., et al. (2002) APP transgenic mice Tg2576 accumulate Abeta peptides that are distinct from the chemically modified and insoluble peptides deposited in Alzheimer’s disease senile plaques. Biochemistry 41, 922–928.
Kang J., Lemaire H. G., Unterbeck A., et al. (1987) The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 325, 733–736.
Kammesheidt A., Boyce F. M., Spanoyannis A. F., et al. (1992) Deposition of β/A4 immunoreactivity and neuronal pathology in transgenic mice overexpressing the carboxyl-terminal fragment of Alzheimer precursor protein in the brain. Proc. Natl. Acad. Sci. USA 89, 10,857–10,861.
Katzman R., Terry R., De Teresa R., Brown T., Davies P., Fuld P., Renbing S., and Peck A. (1988) Clinical, pathological and neurochemical changes in dementia: a subgroup with preserved mental status and numerous senile plaques. Ann. Neurol. 23, 138–144.
Kawabata S., Higgins G. A., and Gordon J. W. (1991) Amyloid plaques, neurofibrillary tangles and neuronal loss in brains of transgenic mice overexpressing the C-terminal fragment of human amyloid precursor protein. Nature 354, 476–478.
King D. L., Arendash G. W, Crawford F., Sterk T., Menendez J., and Mullan M. J. (1999) Progressive and gender-dependent cognitive impairment in the APP(SW) transgenic mouse model for Alzheimer’s disease. Behav. Brain Res. 103, 145–162.
Kitaguchi N., Takahashi Y., Tokushima Y., Shiojiro S., and Ito H. (1988) Novel precursor of Alzheimer’s disease amyloid protein show protease inhibitory activity. Nature 331, 530–532.
Klein W. L., Krafft G. A., and Finch C. E. (2001) Targeting small Aβ oligomers: the solution to an Alzheimer’s disease conundrum? Trends Neurosci. 24, 219–224.
Kosic K. S. (1999) A notable cleavage: Winding up with β-amyloid. Proc. Natl. Acad. Sci USA. 96, 2574–2576.
Kuo Y. M., Kokjohn T. A., Beach T. G., et al. (2001) Comparative analysis of amyloid-beta chemical structure and amyloid plaque morphology of transgenic mouse and Alzheimer’s disease brains. J. Biol. Chem. 276, 12,991–12,998.
Lambert M. P., Barlow A. K., Chromy B. A., et al. (1998) Diffusible, nonfibrillar ligands derived from Abeta1–42 are potent central nervous system neurotoxins. Proc. Natl. Acad. Sci. USA 95, 6448–6453.
Larson J., Lynch G., Games D., and Seubert P. (1999) Alterations in synaptic transmission and long-term potentiation in hippocampal slices from young and aged PDAPP mice. Brain Res. 840, 23–35.
Lee V. M., Balin B. J., Otvos L. Jr., and Trojanowski J. Q. (1991) A68: a major subunit of paired helical filaments and derivatized forms of normal Tau. Science 251, 675–678.
Lemere C. A., Lopera F., Koski K. S., et al. (1996) The E280A presenilin 1 Alzheimer mutation produces increased Aβ42 deposition and severe cerebellar pathology. Nature Med. 2, 1146–1150.
Lendon C. L., Ashall F., and Goate A. M. (1997) Exploring the aetiology of Alzheimer disease using molecular genetics. JAMA 277, 825–831.
Levy-Lahad E., Wijsman E. M., Nemens E., et al. (1995a) A familial Alzheimer’s disease locus on chromosome 1. Science 269, 970–973.
Levy-Lahad E., Wasco W., Poorkaj P., et al. (1995b) Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science 269, 973–977.
Lewis J., Dickson D. W., Lin W. L., et al. (2001) Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 293, 1487–1491.
Lim G. P., Yang F., Chu T., et al. (2000) Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer’s disease. J. Neurosci. 20, 5709–5714.
Lim G. P., Chu T., Yang F., Beech W., Frautschy S. A., and Cole G. M. (2001) The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J. Neurosci. 21, 8370–8377.
Loo D. T., Copani A., Pike C. J., Whittemore E. R., Walencewicz A. J., and Cotman C. W. (1993) Apoptosis is induced by beta-amyloid in cultured central nervous system neurons. Proc. Natl. Acad. Sci. USA 90, 7951–7955.
Loring J. F., Wen X., Lee J. M., Seilhamer J., and Somogyi R. (2001) A gene expression profile of Alzheimer’s disease. Cell Biol. 20, 683–695.
Lue L. F., Kuo Y. M., Roher A. E., et al. (1999) Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer’s disease. Am. J. Pathol. 155, 853–862.
MacGibbon G., Lawlor P., Walton M., et al. (1997) Expression of Fos, Jun and Krox family proteins in Alzheimer’s disease. Exp. Neurol. 147, 316–332.
Malin D. H., Crothers M. K., Lake J. R., et al. (2001) Hippocampal injections of amyloid beta-peptide 1–40 impair subsequent one-trial/day reward learning. Neurobiol. Learn. Mem. 76, 125–137.
Mandelkow E. M. and Mandelkow E. (1998) Tau in Alzheimer’s disease. Trends Cell Biol. 8, 425–427.
Mangoni A., Grassi M. P., Frattola L., Piolti R., Bassi S., Motta A., Marcone A., and Smirne S. (1991) Effects of a MAO-B inhibitor in the treatment of Alzheimer’s disease. Eur. Neurol. 31, 100–107.
Masliah E., Sisk A., Mallory M., Mucke L., Shenk D., and Games D. (1996) Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F β-amyloid precursor protein and Alzheimer’s disease. J. Neurosci. 16, 5795–5811.
Mattson M. P. (1997) Cellular actions of β-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol. Rev. 77, 1081–1132.
Mattson M. P. (2000) Apoptosis in neurodegenerative disorders. Nature Rev. Mol. Cell. Biol. 1, 120–129.
Mattson M. P, Duan W., Lee J., and Zhihong G. (2001) Suppression of brain aging and neurodegenerative disorders by dietary restriction and environmental enrichment: molecular mechanisms. Mech. Aging Dev. 122, 757–778.
Maurice T., Lockhart B. P., and Privat A. (1996) Amnesia induced in mice by centrally administered beta-amyloid peptides involves cholinergic dysfunction. Brain Res. 706, 181–193.
Maurice T., Su T. P., and Privat A. (1998) Sigma1 (sigma 1) receptor agonists and neurosteroids attenuate β25–35-amyloid peptide-induced amnesia in mice through a common mechanism. Neuroscience 83, 413–428.
McDonald M. P., Dahl E. E., Overmier J. B., Mantyh P., and Cleary J. (1994) Effects of an exogenous β-amyloid peptide on retention for spatial learning. Behav. Neural Biol. 62, 60–67.
McDonald M. P., Overmier J. B., Bandyopadhyay S., Babcock D., and Cleary J. (1996) Reversal of β-amyloid-induced retention deficit after exposure to training and state cues. Neurobiol. Learn. Mem. 65, 35–47.
McDonald M. P. and Ovemier J. B. (1998) Present imperfect: A critical review of animal models of the mnemonic impairments in Alzheimer’s disease. Neurosci. Biobehav. Rev. 22, 99–120.
McGeer P. L. and McGeer E. G. (1998) Glial cell reactions in neurodegenerative diseases: pathophysiology and therapeutic interventions. Alzheimer Dis. Assoc. Disord. 12, Suppl 2:S1-S6.
McGeer P. L. and McGeer E. G. (2001) Inflammation, autotoxicity and Alzheimer disease. Neurobiol. Aging 22, 799–809.
Mesulam M. M. (1999) Neuroplasticity failure in Alzheimer’s disease: bridging the gap between plaques and tangles. Neuron 24, 521–529.
Moechars D., Dewachter I., Lorent K., et al. (1999) Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain. J. Biol. Chem. 274, 6483–6492.
Mohs R., Breitner J., Silverman J., and Davis K. L. (1987) Alzheimer’s disease-morbid risk among first degree relatives approximates 50% by 90 years of age. Arch. Gen. Psychiatry 44, 405–408.
Moran P. M., Higgins L. S., Cordell B., and Moser P. C. (1995) Age-related learning deficits in transgenic mice expressing the 751-amino acid isoform of human beta-amyloid precursor protein. Proc. Natl. Acad. Sci. USA 92, 5341–5345.
Morgan D., Diamond D. M., Gottschall P. E., et al. (2000) Aβ peptide vaccination prevents the memory loss in an animal model of Alzheimer’s disease. Nature 408, 982–985.
Morris J. C., McKeel D., Stordandt M., Rubin E. H., Price J. L., Grant E. A., Ball M. J., and Berg L. (1991) Very mild Alzheimer’s disease: information based clinical, psychometric, and pathological distinction from normal aging. Arch. Neurol. 12, 295–312.
Morris J. C. (1993) The clinical dementia rating (CDR): current version and scoring rules. Neurology 43, 2141–2414.
Morris J. C., Stordandt M., McKeel D. W., Rubin E. H., Price J. L., Grant E. A., and Berg L. (1996) Cerebral amyloid deposition and diffuse plaques in “normal” aging: evidence for presymptomatic and very mild Alzheimer’s disease. Neurology 46, 707–719.
Mucke L., Masliah E., Johnson W. B., et al. (1994) Synaptotrophic effects of human amyloid protein precursors in the cortex of transgenic mice. Brain Res. 666, 151–167.
Mucke L., Masliah E., Yu G-Q., et al. (2000) High level neuronal expression of Aβ1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J. Neurosci. 20, 4050–4058.
Mudher A. and Lovestone S. (2002) Alzheimer’s disease-do tauists and baptists finally shake hands? Trends Neurosci. 25, 22–26.
Mullan M., Crawford F., Axelman K., Houlden H., Lilus L., Winblad B., and Lannfelt L. (1992) A pathogenic mutation for probable Alzheimer’s disease in the APP gene at the N-terminus of β-amyloid. Nature Genet. 1, 345–347.
Murrell J., Farlow B., Ghetti B., and Benson MD. (1991) A mutation in the amyloid precursor protein associated with hereditary Alzheimer’s disease. Science 254, 97–99.
Nabeshima T. and Nitta A. (1994) Memory impairment and neuronal dysfunction induced by β-amyloid protein in rats. Tohoku J. Exp. Med. 174, 241–249.
Nakamura S., Murayama N., Noshita T., Annoura H., and Ohno T. (2001) Progressive brain dysfunction following intracerebral infusion of beta(1–42) amyloid peptide. Brain Res. 912, 128–136.
Nalbantoglu J., Tirado-Santiago G., Lahsïni A., et al. (1997) Impaired learning and LTP in mice expressing the carboxy terminus of the Alzheimer amyloid precursor protein. Nature 387, 500–505.
Naruse S., Thinakaran G., Luo J. J., et al. (1998) Effects of PS1 deficiency on a membrane protein trafficking in neurons. Neuron 21, 1213–1221.
Naslund J., Haroutunian V., Mohs R., Davis K. L., Davies P., Greengard P., and Buxbaum J. D. (2000) Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline. JAMA 283, 1571–1577.
Nitta A., Itoh A., Hasegawa T., and Nabeshima T. (1994) β-amyloid protein-induced Alzheimer’s disease animal model. Neurosci. Lett 170, 63–66.
Nitta A., Fukuta T., Hasegawa T., and Nabeshima T. (1997) Continuous infusion of beta-amyloid protein into the rat cerebral ventricle induces learning impairment and neuronal and morphological degeneration. Jpn. J. Pharmacol. 73, 51–57.
O’Hare E., Weldon D. T., Mantyh P. W., et al. (1999) Delayed behavioral effects following intrahippocampal injection of aggregated A beta (1–42). Brain Res. 815, 1–10.
Ohyagi Y. and Tabira T. (1993) Effect of growth factors and cytokines on expression of amyloid beta protein precursor mRNAs in cultured neural cells. Brain Res. Mol. Brain Res. 18, 127–132.
Pallitto M. M. and Murphy R. M. (2001) A mathematical model of the kinetics of β-amyloid fibril growth from the denatured state. Biophys. J. 81, 1805–1822.
Paresce D. M., Chung H., and Maxfield F. R. (1997) Slow degradation of aggregates of the Alzheimer’s disease amyloid beta-protein by microglial cells. J. Biol. Chem. 272, 29,390–29,397.
Pasinetti G. M. (2001) Use of cDNA microarray in the search for molecular markers involved in the onset of Alzheimer’s disease dementia. J. Neurosci. Res. 15, 471–476.
Pike C. J., Walencewicz A. J., Glabe C. G., and Cotman C. W. (1991) Aggregation-related toxicity of synthetic beta-amyloid protein in hippocampal cultures. Eur. J. Pharmacol. 207, 367–368.
Pike C. J., Burdick D., Walencewicz A. J., Glabe C. G., and Cotman C. W. (1993) Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state. J. Neurosci. 13, 1676–1687.
Pompl P. N., Mullan M. J., Bjugstad K., and Arendash G. W. (1999) Adaptation of the circular platform spatial memory task for mice: use in detecting cognitive impairment in the APP(SW) transgenic mouse model for Alzheimer’s disease. J. Neurosci. Methods 87, 87–95.
Probst A., Gotz J., Wiederhold K. H., et al. (2000) Axonopathy and amyotrophy in mice transgenic for human four-repeat tau protein. Acta Neuropathol. (Berl). 99, 469–481.
Prolla T. A. and Mattson M. P. (2001) Molecular mechanisms of brain aging and neurodegenerative disorders: lessons from dietary restriction. Trends Neurosci. Suppl. 24, S21-S31.
Puolivali J., Wang J., Heikkinen T., Heikkila M., Tapiola T., van Groen T., and Tanila H. (2002) Hippocampal Abeta42 levels correlate with spatial memory deficits in APP and PS1 double transgenic mice. Neurobiol. Dis. 9, 339–347.
Qiao X., Cummins D. J., and S.M Paul. (2001) Neuroinflammation-induced acceleration of amyloid deposition in the APPV717F transgenic mouse. Eur. J. Neurosci. 14, 474–482.
Quon D., Wang Y., Catalano R., Scardina J. M., Murakami K., and Cordell B. (1991) Formation of β-amyloid protein deposits in brains of transgenic mice. Nature 352, 239–241.
Rapoport S. I. (1999) In vivo PET imaging and post mortem studies suggest potential reversible and irreversible stages of failure in Alzheimer’s disease. Eur. Arch. Psychiat. Clin. Neurosci. (Suppl) 249, 46–55.
Reisberg B., Ferris S. H., de Leon M. J., and Crook T. (1982) The Global Deterioration Scale for assessment of primary degenerative dementia. Am. J. Psychiat. 139, 1136–1139.
Rogaev E. I., Sherrington R., Rogaev E. A., et al. (1995) Familial Alzheimer’s disease in kindred’s with missense mutations in a gene on chromosome 1 related to the Alzheimer’s disease type3 gene. Nature 376, 775–778.
Roher A. E., Chaney M. O., Kuo Y. M., et al. (1996) Morphological and toxicity of Abeta-(1–42) dimer derived from neuritic and vascular amyloid deposits of Alzheimer’s disease. J. Biol. Chem. 271, 20,631–20,635.
Roses A. (1994) Apolipoprotein E affects the rate of Alzheimer disease expression: β-amyloid burden is a secondary consequence dependent on APOE genotype and duration of disease. J. Neuropathol. Exp Neurol. 53, 429–437.
Roses A. D. (1995) Apolipoprotein E genotyping in differential diagnosis, not prediction of Alzheimer’s disease. Ann. Neurol. 38, 6–14.
Sabo T., Lomnitski L., Nyska A., Beni S., Maronpot R. R., Shohami E., Roses A. D., and Michaelson D. M. (2000) Susceptibility of transgenic mice expressing human apolipoprotein E to closed head injury: the allele E3 is neuroprotective whereas E4 increases fatalities. Neuroscience 101, 879–84.
Sandhu F. A., Salim M., and Zain S. B. (1991) Expression of the human β-amyloid protein of Alzheimer’s disease specifically in brains of transgenic mice. J. Biol. Chem. 266, 21,331–21,334.
Sano M., Ernesto C., Thomas R. G., et al. (1997) A controlled trial of selegiline, alpha-tocopherol, or both and treatment for Alzheimer’s disease. The Alzheimer’s disease cooperative study. N. Engl. J. Med. 336, 1216–1222.
Schellenberg G. D., Pericak-Vance M. A., Wijsman E. M., et al. (1991) Linkage analysis of familial Alzheimer disease, using chromosome 21 markers. Am. J. Hum. Genet. 48, 563–583.
Scheuner D., Eckman C., Jensen M., et al. (1996) Secreted amyloid β-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nature Med. 2, 864–870.
Schonberger S. J., Edgar P. F., Kydd R., Faull R. L., and Cooper G. J. (2001) Proteomic analysis of the brain in Alzheimer’s disease: molecular phenotype of a complex disease process. Proteomics 1, 1519–1528.
Selkoe D. J. (1999) Translating cell biology into therapeutic advances in Alzheimer’s disease. Nature 399, A23-A31.
Serpell L. C. (2000) Alzheimer’s amyloid fibrils: structure and assembly. Biochim. Biophys. Acta. 1502, 16–30.
Sherrington R., Rogaev E. I., Liang Y., et al. (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature 375, 754–760.
Sigurdsson E. M., Hejna M. J., Lee J. M., and Lorens S. A. (1995) beta-Amyloid 25–35 and/or quinolic acid injections into the basal forebrain of young male Fischer-344 rats: behavioral, neurochemical and histological effects. Behav. Brain Res. 72, 141–156.
Sisodia S. S., Annaert W., Kim S-H., and De Strooper B. (2001) γ-secretase: never more enigmatic. Trends Neurosci 11 (Suppl) S2-S5.
Small D. H., Nurcombe V., Reed G., Clarris H., Moir R., Beyreuther K., and Masters C. L. (1994) A heparin-binding domain in the amyloid precursor of Alzheimer’s disease is involved in the regulation of neurite outgrowth. J. Neurosci. 14, 2117–2127.
Small D. H., Mok S. S., and Bornstein J. C. (2001) Alzheimer’s disease and Aβ toxicity: from top to bottom. Nature Rev. Neurosci. 2, 595–598.
Smith J. D., Sikes J., and Levin J. A. (1998a) Human apolipoprotein E allele-specific brain expressing transgenic mice. Neurobiol. Aging 19, 407–413.
Smith D. H., Nakamura M., McIntosh T. K., et al. (1998b) Brain trauma induces massive hippocampal neuron death linked to a surge in β-amyloid levels in mice overexpressing mutant amyloid precursor protein. A. J. Pathol. 153, 1005–1010.
Snowdon D. A., Kemper S. J., Mortimer J. A., Greiner L. H., Wekstein D. R., and Markesbery W. R. (1996) Linguistic ability in early life and cognitive function and Alzheimer’s disease in late life. Findings from the Nun Study. JAMA 275, 528–532.
Soriano S., Lu D. C., Chandra S., Pietrzik C. U., and Koo E. H. (2001) The amyloidogenic pathway of amyloid precursor protein (APP) is independent of its cleavage by caspases. J. Biol. Chem. 276, 29,045–29,050.
Spillantini M. G., Bird T. D., and Ghetti B. (1998) Frontotemporal dementia and Parkinsonism linked to chromosome 17: a new group of tauopathies. Brain Pathol. 8, 387–402.
Spittaels K., Van den Haute C., Van Dorpe J., et al. (1999) Prominent axonopathy in the brain and spinal cord of transgenic mice overexpressing four-repeat human tau protein. Am. J. Pathol. 155, 2153–2165.
Stadelmann C., Deckwerth T. L., Srinivasan A., Bancher C., Bruck W., Jellinger K., and Lassmann H. (1999) Activation of caspase-3 in single neurons and autophagic granules of granulovacuolar degeneration in Alzheimer’s disease. Evidence for apoptotic cell death. Am. J. Pathol. 155, 1459–1466.
Stein T. D. and Johnson J. A. (2002) Lack of neurodegeneration in transgenic mice over expressing mutant amyloid precursor protein is associated with increased levels of transthyretin and the activation of cell survival pathways. J. Neurosci. 22, 7380–7388.
Stéphan A., Laroche S., and Davis S. (2001) Generation of aggregated beta-amyloid in the rat hippocampus impairs synaptic transmission and plasticity and causes memory deficits. J Neurosci. 12, 5703–5714.
Stéphan A., Davis S., Salin H., Dumas S., Mallet J., and Laroche S. (2002a) Age-dependent differential regulation of genes encoding APP and α-synuclein in hippocampal synaptic plasticity. Hippocampus 12, 55–62.
Stéphan A., Laroche S., and Davis S. (2003) Learning deficits and dysfunctional synaptic plasticity induced by aggregated amyloid peptides in the dentate gyrus are rescued by chronic treatment with indomethacin. Eur. J. Neurosci. 17, 1921–1927.
Stern Y., Gurland B., Tatemichi T. K., Tang M. X., Wilder D., and Mayeux R. (1994) Influence of education and occupation on the incidence of Alzheimer’s disease. JAMA 271, 1004–1010.
Stewart W. F., Kawas C., Corrada M., and Metter E. J. (1997) Risk of Alzheimer’s disease and duration of NSAID use. Neurology 48, 626–632.
Strittmatter W. J., Saunders A. M., Schmehel D., Pericak-Vance M. A., Enghild J., Salvesen G. S., and Roses A. D. (1993) Apolipoprotein E: high-avidity binding to β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer’s disease. Proc. Natl. Acad. Sci USA 90, 1977–1981.
Strohmeyer R. and Rogers J. (2001) Molecular and cellular mediators of Alzheimer’s disease inflammation. J. Alzheimer’s Disease 3, 131–157.
Sturcher-Pierrat C., Abramowski D., Duke M., et al. (1997) Two amyloid precursor protein transgenic models with Alzheimer disease-like pathology. Proc. Natl. Acad. Sci. USA 94, 13,287–13,292.
Sun M. K. and Alkon D. L. (2002) Impairment of hippocampal CA1 heterosynaptic transformation and spatial memory by beta-amyloid(25–35). J. Neurophysiol. 87, 2441–2449.
Sweeney W. A., Luedtke J., McDonald M. P., and Overmier J. P. (1997) Intrahippocampal injections of exogenous beta-amyloid induces postdelay errors in an eight-arm radial maze. Neurobiol. Learn. Mem. 68, 97–101.
Takashima A., Noguchi K., Sato K., Hoshino T., and Imahori K. (1993) Tau protein kinase I is essential for amyloid beta-protein-induced neurotoxicity. Proc. Natl. Acad. Sci. USA 90, 7789–7793.
Takashima A., Murayama M., Murayama O., et al. (1998a) Presenilin 1 associates with glycogen synthase kinase-3beta and its substrate tau. Proc. Natl. Acad. Sci. USA 95, 9637–9641.
Takashima A., Honda T., Yasutake K., et al. (1998b) Activation of tau protein kinase I/glycogen synthase kinase-3beta by amyloid beta peptide (25–35) enhances phosphorylation of tau in hippocampal neurons. Neurosci. Res. 31, 317–323.
Tanzi R. E., Vaula G., Romano D. M., et al. (1992) Assessment of amyloid beta-protein precursor gene mutations in a large set of familial and sporadic Alzheimer disease cases. Am. J. Hum. Genet. 51, 273–282.
Teasdale G. M., Nicoll J. A., Murray G., and Fiddes M. (1997) Association of apolipoprotein E polymorphism with outcome after head injury. Lancet 350, 1069–1071.
Terranova J. P., Kan J. P., Storme J. J., Perreaut P., Le Fur G., and Soubrie P. (1996) Administration of amyloid beta-peptides in the rat medial septum causes memory deficits: reversal by SR 57746A, a non peptide neurotrophic compound. Neurosci. Lett. 213, 79–82.
Terry R. D., Masliah E., Salmon D. P., Butters N., DeTeresa R., Hill R., Hansen L. A., and Katzman R. (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synaptic loss is the major correlate of cognitive impairment. Ann. Neurol. 30, 572–580.
Tesseur I., Van Dorpe J., Bruynseels K., Bronfman F., Sciot R., Van Lommel A., and Van Leuven F. (2000) Prominent axonopathy and disruption of axonal transport in transgenic mice expressing human apolipoprotein E4 in neurons of brain and spinal cord. Am J Pathol. 157, 495–510.
Tomiyama T., Shoji A., Kataoka K., Suwa Y., Asano S., Kaneko H., and Endo N. (1996) Inhibition of amyloid beta protein aggregation and neurotoxicity by rifampicin. Its possible function as a hydroxyl radical scavenger. J. Biol. Chem. 271, 6839–6844.
Troncoso J. C., Martin L. J., Dal Forno G., and Kawas C. H. (1996) Neuropathology in controls and demented subjects from the Baltimore Longitudinal Study of Aging. Neurobiol. Aging 17, 365–371.
Tsuji T. and Shimohama S. (2001) Analysis of the proteomic profiling of brain tissue in Alzheimer’s disease. Dis. Markers 17, 247–257.
Uryu K., Laurer H., McIntosh T., Pratico D., Martinez D., Leight S., Lee V.M-Y., and Trojanowski J. Q. (2002) Repetitive mild brain trauma accelerates Aβ deposition, lipid peroxidation, and cognitive impairment in a transgenic mouse model of Alzheimer amyloidosis. J. Neurosci. 22, 446–454.
Vassar R., Bennett B., Babu-Khan S., et al. (1999) Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembranal aspartic protease BACE. Science 286, 735–741.
Vassar R. and Citron C. (2000) Aβ-generating enzymes: recent advances in β-and γ-secretase research. Neuron 27, 419–422.
Walker D. G., Lue L. F., and Beach T. G. (2001) Gene expression profiling of amyloid beta peptide-stimulated human post-mortem brain microglia. Neurobiol. Aging 22, 957–966.
Walsh D. M., Hartley D. M., Kusumoto Y., et al. (1999) Amyloid beta-protein fibrillogenesis. Structure and biological activity of protofibrillar intermediates. J. Biol. Chem. 274, 25,945–25,952.
Walsh D. M., Klyubin I., Fadeeva J. V., Cullen W. K., Anwyl R., Wolke M. S., Rowan M. J., and Selkoe D. J. (2002) Naturally secreted oligomers of amyloid b protein potently inhibit hippocampal long-term potentiation iv vivo. Nature 416, 535–539.
Wang R., Sweeney D., Gandy S. E., and Sisodia S. S. (1996) The profile of soluble amyloid beta protein in cultured cell media. Detection and quantification of amyloid beta protein and variants by immunoprecipitation-mass spectrometry. J. Biol. Chem. 271, 31,894–31,902.
Wang J., Dickson D. W., Trojanowski J. Q., and Lee V. M. (1999) The levels of soluble versus insoluble brain Abeta distinguish Alzheimer’s disease from normal and pathologic aging. Exp. Neurol. 158, 328–337.
Wang H-W., Pasternak J. F., Kuo H., et al. (2002) Soluble oligomer of β amyloid (1–42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus. Brain Res. 924, 133–140.
Weldon D. T., Rogers S. D., Ghilardo J. R., et al. (1998) Fibrillar β-amyloid induces microglial phagocytosis, expression of inducible nitric oxide synthase, and loss of a select population of neurons in the rat CNS in vivo. J. Neurosci. 18, 2161–2173.
Westerman M. A., Cooper-Blacketer D., Mariash A., et al. (2002) The relation ship between Aβ and memory in the Tg2576 mouse model of Alzheimer’s disease. J. Neurosci. 22, 1858–1867.
White F., Nicoll J. A. R., Roses A. D., and Horburgh K. (2001) Impaired neuronal plasticity in transgenic mice expressing human Apolipoprotein E4 compared to E3 in a model of entorhinal cortex lesion. Neurobiol. Dis. 8, 611–625.
Winkler J., Connor D. J., Frautschy S. A., Behl C., Waite J. J., Cole G. M., and Thal L. J. (1994) Lack of long-term effects after beta-amyloid protein injections in rat brain. Neurobiol. Aging 15, 601–607.
Wirak D. O., Bayner R., Ramabhadran T. V., et al. (1991) Deposits of amyloid β protein in the central nervous system of transgenic mice. Science 253, 323–325.
Wisniewski T., Castano E. M., Golabek A., Vogel T., and Frangione B. (1994) Acceleration of Alzheimer’s fibril formation by apolipoprotein E in vitro. Am. J. Pathol. 145, 1030–1035.
Wolfe M., Xia W., Ostaszewski B. L., Diehl T. S., Kimberley W. T., and Selkoe D. J. (1999) Two transmembrane aspartates in presenilin-1 required for endoproteolysis and γ-secretase activity. Nature 398, 513–517.
Wolozin B., Iwasaki K., Vito P., et al. (1996) Participation of presenilin 2 in apoptosis: enhanced basal activity conferred by an Alzheimer mutation. Science 274, 1710–1713.
Wong P. C., Zheng H., Chen H., et al. (1997) Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm. Nature 378, 288–292.
Yamada K., Tanaka T., Han D., Senzaki K., Kameyama T., and Nabeshima T. (1999) Protective effects of idebonone and alpha-tocopherol on beta-amyloid-(1-42)-induced learning and memory deficits in rats: implication of oxidative stress in beta-amyloid-induced neurotoxicity in vivo. Eur. J. Neurosci. 11, 83–90.
Yamaguchi Y. and Kawashima S. (2001) Effects of amyloid-beta-(25–35) on passive avoidance, radial-arm maze learning and choline acetyl-transferase activity in the rat. Eur. J. Pharmacol. 412, 265–272.
Yan J. J., Cho J. Y., Kim K. L., Jung J. S., Huh S. O., Kim Y. H., and Song D. K. (2001) Protection against beta-amyloid peptide toxicity in vivo with long-term administration of ferulic acid. Br. J. Pharmacol. 133, 89–96.
Yan S. D., Chen X., Fu J., et al. (1996) RAGE and amyloid β peptide neurotoxicity in Alzheimer’s disease. Nature 382, 685–692.
Younkin S. G. (1995) Evidence that A beta 42 is the real culprit in Alzheimer’s disease. Ann. Neurol. 37, 287–288.
Yu G., Nishimura M., Arawaka S., et al. (2000) Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing. Nature 407, 48–54.
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Davis, S., Laroche, S. What can rodent models tell us about cognitive decline in alzheimer’s disease?. Mol Neurobiol 27, 249–276 (2003). https://doi.org/10.1385/MN:27:3:249
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DOI: https://doi.org/10.1385/MN:27:3:249