Background: Alzheimer’s disease is a severe neurodegenerative brain disorder, showing
severe beta-amyloid depositions in the brain (plaques) and in vessels (cerebral amyloid angiopathy,
CAA), tau pathology, neurodegeneration (and loss of acetylcholine), inflammation with reactive
astrocytes and microglia and cerebrovascular damage, all resulting in memory loss.
Methods And Results: In this review, I present a hypothesis that chronic vascular lesions and bleedings
cause platelet overactivation and repair. Platelets express large amounts of amyloid precursor
protein (APP) and release beta-amyloid, possibly playing a role as a clotting substance. As the
number of bleedings increases over lifetime, the function of platelets diminishes until they are
dysfunctional. Dysfunctional processing of APP in platelets and subsequent inflammatory processes
may play a role in the formation of CAA. Local lesions and acidosis may transfer a pathological
cascade including silent strokes into the brain, causing irreversible APP dysfunction, tau dysregulation
and beta-amyloid deposition.
Conclusion: Platelets may play a central role in the processing of plaque deposition in the
Alzheimer brain and may be of interest for diagnostic as well as therapeutic strategies.