In Alzheimer disease, the tau protein forms neurofibrillary tangles (NFTs). The specific biochemical change to tau that causes its aggregation is:

• A Ubiquitination of tau preventing its proteasomal degradation
• B Glycation of tau by advanced glycation end-products in diabetic patients
• C Cleavage of tau by gamma-secretase generating toxic C-terminal fragments
• D Hyperphosphorylation of tau causing it to dissociate from microtubules and aggregate into paired helical filaments ✓

Explanation

Tau is normally a microtubule-stabilizing protein. In Alzheimer disease, tau becomes abnormally hyperphosphorylated (by kinases including CDK5 and GSK-3beta), reducing its affinity for microtubules. Dissociated hyperphosphorylated tau self-assembles into paired helical filaments (PHFs) that form neurofibrillary tangles, disrupting axonal transport. Gamma-secretase cleaves APP to generate Abeta, not tau.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.