Alzheimer disease: plaques and tangles
- Lesion
Alzheimer disease is the commonest cause of dementia: amyloid plaques build up between neurons and tau tangles form inside them.
What it is
Alzheimer disease is a slowly progressive dementia that starts with memory loss. Its pathology is the combination of extracellular amyloid-beta plaques, intracellular tau neurofibrillary tangles, synapse and neuron loss and cerebral amyloid angiopathy. Amyloid-beta comes from abnormal cleavage of amyloid precursor protein (APP). Most cases are sporadic and late, with APOE ε4 as the main genetic risk; rare early-onset families carry APP, PSEN1 or PSEN2 mutations, and people with Down syndrome develop it early because they have three copies of APP.
Structure
- Silver stains and amyloid-beta and tau immunostains show plaques and tangles; Congo red stains plaque cores and vascular amyloid.
- Other lesions: granulovacuolar degeneration and Hirano bodies in hippocampal neurons.
- Neuropathologic diagnosis combines amyloid phase, tangle stage and neuritic plaque score (ABC score).
Step by step
- APP in the neuronal membrane is cleaved by beta-secretase, then gamma-secretase.
- Amyloid-beta peptides are released and some misfold into oligomers.
- Oligomers harm synapses; fibrils form plaques and coat vessel walls.
- Amyloid accelerates tau hyperphosphorylation; tau leaves microtubules and forms tangles.
- Tau pathology spreads along circuits from the entorhinal cortex outward.
- Synapses and neurons are lost and cognition declines.
The genes of Alzheimer disease
| Gene | Chromosome | Effect | Onset |
|---|---|---|---|
| APP | 21 | More or stickier amyloid-beta; extra copy in Down syndrome | Early |
| PSEN1 | 14 | Altered gamma-secretase, more amyloid-beta 42 | Early, most common familial cause |
| PSEN2 | 1 | Altered gamma-secretase | Early |
| APOE ε4 | 19 | Impairs amyloid clearance; risk allele | Late, earlier with two copies |
Clinical notes
- Memory loss for recent events, then language, visuospatial and executive problems; death often follows infection years later.
- Anti-amyloid antibodies can cause brain swelling and microbleeds (amyloid-related imaging abnormalities), more so in APOE ε4 carriers. In Antioquia, Colombia, a large family with the PSEN1 E280A mutation has been central to Alzheimer research.
Test yourself
Think of the answer, then tap the question to see it.
What is a neuritic plaque?
An extracellular deposit with an amyloid-beta core surrounded by swollen dystrophic neurites and reactive glia.
Why do people with Down syndrome develop Alzheimer disease early?
They have three copies of chromosome 21, which carries the APP gene, so they make more amyloid-beta.
Which allele is the main genetic risk factor for late-onset Alzheimer disease?
APOE ε4.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Alzheimer Disease (StatPearls (NCBI Bookshelf), 2026).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.