The pathognomonic neuropathological triad of Alzheimer disease includes neurofibrillary tangles, senile plaques, and granulovacuolar degeneration. Neurofibrillary tangles are composed primarily of:
- A Beta-amyloid peptide (Aβ42) aggregated into beta-pleated sheets
- B Hyperphosphorylated tau protein forming paired helical filaments ✓
- C Alpha-synuclein protein forming Lewy body-like inclusions
- D TDP-43 protein forming ubiquitinated inclusions in frontotemporal dementia
Explanation
Neurofibrillary tangles (NFTs) are intraneuronal inclusions composed of paired helical filaments (PHFs) made of hyperphosphorylated tau protein. Normally, tau stabilizes microtubules; when abnormally hyperphosphorylated (by kinases including CDK5 and GSK-3β), tau detaches from microtubules, disrupting axonal transport and aggregating into PHFs. NFTs correlate better with cognitive decline and neuronal loss than amyloid plaques. Senile plaques contain extracellular Aβ42 peptide; alpha-synuclein is the major component of Lewy bodies in Parkinson disease; TDP-43 inclusions characterize ALS and FTLD-TDP.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.