Alzheimer's disease - neuropathological hallmarks (amyloid plaques, tau tangles)
Core concept
Two hallmarks - always name both
- Extracellular amyloid-beta plaques (neuritic/senile)
- APP cut by beta-secretase (BACE1) then gamma-secretase (presenilin 1/2) -> Abeta42 -> aggregates
- The non-amyloidogenic route uses alpha-secretase, which cuts within the Abeta sequence and destroys it
- Intracellular neurofibrillary tangles - hyperphosphorylated tau in paired helical filaments
- Tau normally stabilises microtubules; hyperphosphorylation detaches it
- Amyloid comes first; tau tracks the clinical picture
- Plaque burden correlates poorly with cognition
- Braak tangle stage and neuronal loss correlate well
- Also present: cerebral amyloid angiopathy, granulovacuolar degeneration, Hirano bodies, synaptic loss, and cholinergic denervation from the nucleus basalis of Meynert
3 more sections, plus exam facts
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