Original ArticlesA sex difference and no effect of ApoE type on the amount of cytoskeletal alterations in the nucleus basalis of Meynert in Alzheimer’s disease
Section snippets
Tissue preparation
Brains of 36 AD patients ranging in age from 49 to 96 years were obtained at autopsy (see Table 1 for details and clinicopathological information). The patients were clinically assessed and diagnosed as “probable AD” by excluding other possible causes of dementia by history, physical examination and laboratory tests according to the diagnostic criteria as described by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders
Immunocytochemistry
In all AD patients immunocytochemical staining with Alz-50 revealed a very intense staining of NBM neuronal perikarya, neuropil threads and some dystrophic neurites (Fig. 1 ). Qualitative microscopic analysis showed that both the area occupied by Alz-50 staining (Alz-50 load) and the proportion of Alz-50-stained neurons in AD patients with the ApoE genotype ϵ3/3 showed much interindividual variation.
Alz-50 load or the total area covered by Alz-50 staining
A total of 5,264 images (each image 37,456 μm2) were analyzed. In order to determine the
Discussion
Earlier studies had shown that the NBM is not only heavily stained by Alz-50, but also by other antibodies showing cytoskeletal alterations. In AD, NBM neurons are, e.g., intensely stained by the 60e (against NFTs), tau-1 (against tau) and 3–39 (against ubiquitin) antibody. However, Alz-50 showed the most intense staining in the NBM of AD patients (48).
Alz-50 not only stains AD changes, but also cell bodies, e.g., in the periventricular nucleus of the hypothalamus of nondemented young controls
Acknowledgements
Brains were obtained from the Netherlands Brain Bank, Amsterdam, The Netherlands (coordinator Dr. R. Ravid). Alz-50 was kindly donated by Abbott Laboratories, Chicago, USA. We thank Dr. C. W. Pool for his essential help with the image analysis system and O. Pach for her secretarial assistance. Much appreciation to Dr. O. S. Jørgenson (Laboratory of Neuropsychiatry, University of Copenhagen, Denmark) for performing ApoE genotyping. The neuropathological diagnosis of Alzheimer’s disease was
References (56)
- et al.
Occurrence of neuropil threads in the senile human brain and Alzheimer’s disease: A third location of paired helical of neurofibrillary tangles and neuritic plaques
Neurosci. Lett.
(1986) - et al.
Abnormal tau phosphorylation at Ser396 in Alzheimer’s recapitulates development and contributes to reduced binding
Neuron
(1993) - et al.
Localization of the Alz-50 epitope in recombinant human microtubule-associated protein tau
Neurosci. Lett.
(1991) Amyloid, the presenilins and Alzheimer’s disease
Trends Neurosci
(1997)- et al.
The disordered neuronal cytoskeleton in Alzheimer’s disease
Curr. Opin. Neurobiol.
(1992) Disruption of the cytoskeleton in Alzheimer’s disease
Curr. Opin. Neurobiol.
(1995)- et al.
Influence of the apolipoprotein E genotype on amyloid deposition and neurofibrillary tangle formation in Alzheimer’s disease
Neuroscience
(1995) - et al.
Apolipoprotein E and Alzheimer’s disease
- et al.
The distribution of Alz-50 immunoreactivity in the normal brain
Neuroscience
(1993) - et al.
Decreased neuronal activity in the nucleus basalis of Alzheimer’s disease as suggested by the size of the Golgi apparatus
Neuroscience
(1994)
Apolipoprotein E epsilon 4 allele distributions in Alzheimer’s disease and in other amyloid-forming diseases
Lancet
HypothesisMicrotubule instability and paired helical filament formation in the Alzheimer disease brain are related to apolipoprotein E genotype
Exp. Neurol.
Tau and ubiquitin in the human hypothalamus in aging and disease
Brain Res
Mechanisms of estrogen action during neural development: Mediation by interactions with the neurotrophins and their receptors
J. Steroid Biochem. Mol. Biol.
The monoclonal antibody Alz-50, used to reveal cytoskeletal changes in Alzheimer’s disease, also reacts with a large subpopulation of somatostatin neurons in the normal hypothalamus and adjoining areas
Brain Res
Apolipoprotein E. binding to soluble Alzheimer’s disease
Biochem. Biophys. Res. Commun.
The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in patients with Alzheimer’s disease
Cereb. Cortex
Neurofibrillary tangles but not senile plaques parallel severity of Alzheimer’s disease
Neurology
Molecular analysis of neurofibrillary degeneration in Alzheimer’s disease
Am. J. Pathol.
Alzheimer’s diseaseTransiently developing dendritic changes in pyramidal cells of sector CA1 of the Ammon’s horn
Acta Neuropathol
Neuropil threads occur in dendrites of tangle-bearing nerve cells
Neuropathol. Appl. Neurobiol.
Incidence of clinically diagnosed subtypes of dementia in an elderly population
Br. J. Psychiatry
A polymorphism in the regulatory region of APOE associated with risk of Alzheimer’s dementia
Nat. Genetics.
The structural basis of monoclonal antibody Alz50’s selectivity for Alzheimer’s disease pathology
J. Biol. Chem.
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Nat. Genet.
Late-onset Alzheimer’s diseaseIncidence data from the Kungsholmen project, Stockholm
A β-peptide length and apolipoprotein E genotype in Alzheimer’s disease
Ann. Neurol.
Clinical and pathological correlates of apolipoprotein E epsilon 4 in Alzheimer’s disease
Ann. Neurol.
Cited by (39)
Women and Alzheimer's disease
2023, COVID-19 in Alzheimer's Disease and DementiaSexual differentiation of the human hypothalamus: Relationship to gender identity and sexual orientation
2021, Handbook of Clinical NeurologyCitation Excerpt :Also in the accelerated aging procedure, i.e., in Alzheimer's disease (AD), which shows pronounced changes in neurofibrillary proteins in the infundibular nucleus and posterior median eminence, neurofibrillary pathology was found in 79% of males over 60 years of age, but in only 6% of females (Schultz et al., 1996). In contrast, we observed more hyperphosphorylated Tau in the nucleus basalis of Meynert of female than of male AD patients (Salehi et al., 1998). Subsequently a large number of structural and functional sex differences have been described in the adult human brain.
The art of matching brain tissue from patients and controls for postmortem research
2018, Handbook of Clinical NeurologyAlterations in the histaminergic system in Alzheimer's disease: A postmortem study
2012, Neurobiology of AgingCitation Excerpt :The nucleus basalis of Meynert (NBM) is the major source of acetylcholine for the cortex (Mesulam et al., 1983). Female AD patients matched for age showed more severe early cytoskeletal alterations (Salehi et al., 1998) in the nucleus basalis of Meynert. Our data, together with previous findings, seem to offer a neurochemical basis for the observation that female AD patients show more pronounced cognitive deficits during the course of their disease (Henderson, 1997).
Gender differences in neurotrophin and glutamate receptor expression in cholinergic nucleus basalis neurons during the progression of Alzheimer's disease
2011, Journal of Chemical NeuroanatomyCitation Excerpt :On the other hand, cholinergic basal forebrain (CBF) nucleus basalis (NB) neurons, a continuum of cholinergic cortical projection neurons that mediate memory and attentional processes (Baxter and Chiba, 1999) and degenerate in AD (Whitehouse et al., 1981), exhibit 35% more NFT-bearing neurons in females than males (Salehi et al., 1998). Furthermore, the number of NFT-bearing NB neurons correlated with Global Dementia Score in these subjects (Salehi et al., 1998). Interestingly, female AD patients performed significantly worse than male patients on language tests of semantic memory and verbal fluency (Buckwalter et al., 1996; Henderson and Buckwalter, 1994).