The amyloid hypothesis of Alzheimer's disease at 25 years

Despite continuing debate about the amyloid β-protein (or Aβ hypothesis, new lines of evidence from laboratories and clinics worldwide support the concept that an imbalance between production and clearance of Aβ42 and related Aβ peptides is a very early, often initiating factor in Alzheimer's disease (AD). Confirmation that presenilin is the catalytic site of γ-secretase has provided a linchpin: all dominant mutations causing early-onset AD occur either in the substrate (amyloid precursor protein, APP) or the protease (presenilin) of the reaction that generates Aβ. Duplication of the wild-type APP gene in Down's syndrome leads to Aβ deposits in the teens, followed by microgliosis, astrocytosis, and…

• W
  Wellcome
• WT
  Wellcome Trust
• AR
  Alzheimer's Research Trust
• NI
  National Institutes of Health

  Award: AG015379
• MR
  Medical Research Council
• NI
  National Institute on Aging

  Awards: AG015379, AG06173