Abstract
Alzheimer’s disease (AD) is a progressive dementing neurodegenerative disorder characterized pathologically by the presence of senile plaques and neurofibrillary changes in the brains of affected individuals (1). Senile plaques are composed of amyloid β peptides (An) comprised of —40 amino acids that are proteolytically produced from ββ-amyloid precursor protein (βAPP). βAPP is initially cleaved by β-secretase to generate a 99-residue C-terminal fragment (C99) that then is cleaved by γ-secretase to generate Aβ. A subset of AD is inherited as an autosomal dominant trait (familial AD: FAD). Genetic mutations in βAPP genes that cosegregate with the clinical manifestations of FAD increase production of the amyloidogenic Aβ42 species ending at Ala42 (2); Aβ42, which normally comprises only ~10% of total secreted Aβ, aggregates much faster than the predominant Aβ40 species (3), and A342 is the initially and predominantly deposited Aβ species in AD brains (4,5). These data implicated a seminal role of Aβ42 in the pathogenesis of AD.
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© 2002 Kluwer Academic / Plenum Publishers, New York
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Iwatsubo, T., Tomita, T., Watabiki, T., Takikawa, R., Morohashi, Y., Takasugi, N. (2002). Presenilin and Amyloidogenesis: A Structure-Function Relationship Study on Presenilin 2. In: Mizuno, Y., Fisher, A., Hanin, I. (eds) Mapping the Progress of Alzheimer’s and Parkinson’s Disease. Advances in Behavioral Biology, vol 51. Springer, Boston, MA. https://doi.org/10.1007/978-0-306-47593-1_11
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DOI: https://doi.org/10.1007/978-0-306-47593-1_11
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