Year: 2016
Type: preprint
Abstract: Alzheimer's disease (AD) is characterized neuropathologically by neuronal cell loss, extracellular neuritic plaques composed of b-amyloid (Ab), and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein.Ab is generated by proteolytic processing of the b-amyloid precursor protein (APP).Most individuals with Down syndrome (DS) have three copies of APP, leading to elevated APP expression, increased Ab deposition, and characteristic AD neuropathology.Sequencing of APP in familial early-onset AD identified missense mutations that cause AD, while a recently discovered coding variant, APP A673T, reduces the risk for AD.Cellular and animal studies show that risk-associated mutations increase total Ab levels, Ab42 levels, or Ab fibrillogenesis, while protective alleles reduce Ab levels.Together, these studies provide compelling evidence for the Ab hypothesis and suggest that therapeutics that reduces Ab levels or Ab fibrillogenesis should lower the risk for or prevent AD.
Authors: Julia TCW, Alison M. Goate
Institution: Icahn School of Medicine at Mount Sinai
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2566006671