Braak staging model

The Braak staging model is a neuropathological system used to classify the progression of Alzheimer’s disease (AD) based on the anatomical distribution of tau neurofibrillary tangles (NFTs) in the brain. It consists of six stages:

• Stages I and II: Tau pathology is confined mainly to the transentorhinal and entorhinal cortex. These stages correspond to preclinical AD, where individuals typically show no or very mild symptoms.
• Stages III and IV: Tau pathology spreads to limbic regions including the hippocampus, associated with prodromal dementia, characterized by mild cognitive impairment and isolated memory deficits.
• Stages V and VI: Extensive tau pathology extends into the neocortex, correlating with fully developed Alzheimer’s dementia and severe cognitive decline.

This Braak system is integrated into contemporary AD diagnostic criteria and corresponds well with clinical manifestations, with symptom onset generally occurring between stages II and IV. PET imaging using tau ligands now allows in vivo application of the Braak framework to monitor disease progression and correlate it with cognitive decline and biomarker changes in living patients.