Abstract
Alzheimer’s disease (AD) is a neurodegenerative disease and the most common form of progressive dementia in the elderly. It is characterized by a progressive loss of memory, declining cognitive function and, ultimately, leads to decreasing physical functions and death. The neuropathological hallmarks of AD are the senile plaques and the neurofibrillary tangles, which are botprotein aggregates deposited in the brain. The neurofibrillary tangles represent intraneuronal bundles of paired helical filaments that mainly consist of the microtubule-associated protein tau in an abnormally phosphorylated form (for review on tau see GOEDERT et al. 1996). The extracellular amyloid plaques mainly consist of the 42-residue-long amyloid β-peptide (Aβ, βA4; GLENNER and WONG 1984; MASTERS et al. 1985), which is proteolytically derived from the much larger amyloid precursor protein (APP, AβPP, βAPP; KANG et al. 1987). The generation and deposition of Aβ seem to be at the origin of the disease and are believed to trigger a complex pathological cascade that causes neuronal dysfunction, the appearance of the neurofibrillary tangles and, finally, the onset of the disease. This current view for the central role of Aβ in the pathogenesis of AD is supported by a wealth of data (for review, see HARDY 1997), including mutations and a polymorphism in four genes that lead to an inherited form or an early-onset form of AD. On the cellular level, these mutations either lead to an enhanced generation of the Aβ-peptide or to an increased rate of its aggregation. Consequently, approaches used to develop a causative therapy for AD try to determine in detail the proteolytic mechanisms that lead to the release of Aβ from APP and the mechanisms of Aβ aggregation and A/3 neurotoxicity (for reviews about Aβ aggregation and neurotoxicity see HARPER and LANSBURY 1997 and YANKNER 1996).
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Lichtenthaler, S.F., Masters, C.L., Beyreuther, K. (2000). Proteolytic Processing of the Amyloid Precursor Protein of Alzheimer’s Disease. In: von der Helm, K., Korant, B.D., Cheronis, J.C. (eds) Proteases as Targets for Therapy. Handbook of Experimental Pharmacology, vol 140. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-57092-6_19
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