Journal
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
Volume 7, Issue 6, Pages -Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/cshperspect.a024539
Keywords
-
Categories
Funding
- National Institute on Aging
- JPB Foundation
- Ronald M. Loeb Center for Alzheimer's Disease
Ask authors/readers for more resources
Alzheimer's disease (AD) is characterized neuropathologically by neuronal cell loss, extracellular neuritic plaques composed of beta-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, A beta 42 levels, or A beta fibrillogenesis, while protective alleles reduce A beta levels. Together, these studies provide compelling evidence for the A beta hypothesis and suggest that therapeutics that reduces A beta levels or Ab fibrillogenesis should lower the risk for or prevent AD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available