[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Central nervous system](https://durgical.com/en/general-pathology/areas/cns/) › Alzheimer disease: plaques and tangles

# 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.

Updated Nov 12, 2026

## Key points

- Gross: cortical atrophy with wide sulci, especially frontal, temporal and parietal; hippocampal atrophy; hydrocephalus ex vacuo.
- Neuritic plaque: amyloid-beta core surrounded by dystrophic neurites; diffuse plaques lack neurites.
- Neurofibrillary tangle: hyperphosphorylated tau in paired helical filaments, flame-shaped in pyramidal neurons; spreads from entorhinal cortex to hippocampus to neocortex (Braak stages).
- APP is cut by beta- and gamma-secretase (presenilin) to make amyloid-beta 42, which aggregates.
- APOE ε4 raises risk and lowers age of onset; ε2 is protective.
- Down syndrome: APP on chromosome 21, early Alzheimer pathology.

## 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](https://durgical.com/en/conditions/down-syndrome/) | 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](https://durgical.com/en/conditions/alzheimer-disease/) | 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.

## Memory aid

Plaques outside, tangles inside, memory goes first because the entorhinal cortex goes first.

## 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.

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## Elsewhere in DurgiPedia

- [The cerebral cortex and language](https://durgical.com/en/physiology/the-cerebral-cortex-and-language/)

## Connections

## Related 7

- [Neurodegeneration: the protein table](https://durgical.com/en/general-pathology/neurodegeneration-the-protein-table/)
- [Small vessel disease: hypertensive and amyloid hemorrhage](https://durgical.com/en/general-pathology/small-vessel-disease-hypertensive-and-amyloid-hemorrhage/)
- [Frontotemporal lobar degeneration](https://durgical.com/en/general-pathology/frontotemporal-lobar-degeneration/)
- [Parkinson disease and Lewy body disorders](https://durgical.com/en/general-pathology/parkinson-disease-and-lewy-body-disorders/)
- [Trisomies 21, 18 and 13, and the 22q11.2 deletion](https://durgical.com/en/general-pathology/trisomies-21-18-and-13-and-the-22q11-2-deletion/)
- [Cellular aging: telomeres, DNA damage, senescence and proteostasis](https://durgical.com/en/general-pathology/cellular-aging-telomeres-dna-damage-senescence-and-proteostasis/)
- [How organs age: normal changes vs disease](https://durgical.com/en/general-pathology/how-organs-age-normal-changes-vs-disease/)

## Related conditions 5

- [Alzheimer disease](https://durgical.com/en/conditions/alzheimer-disease/)
- [Dementia (major neurocognitive disorder)](https://durgical.com/en/conditions/dementia/)
- [Down syndrome (trisomy 21)](https://durgical.com/en/conditions/down-syndrome/)
- [Amyloidosis](https://durgical.com/en/conditions/amyloidosis/)
- [Vascular dementia](https://durgical.com/en/conditions/vascular-dementia/)

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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](https://www.ncbi.nlm.nih.gov/books/NBK499922/) (StatPearls (NCBI Bookshelf), 2026).

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Representative model, for educational purposes only.

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