On brain autopsy of a patient with advanced Alzheimer disease, the neuropathological staging system (Braak and Braak stages) classifies neurofibrillary tangle (NFT) distribution in which order?

• A Frontal lobe → temporal lobe → occipital lobe
• B Substantia nigra → striatum → cortex
• C Entorhinal cortex → hippocampus/limbic → neocortex (transentorhinal to neocortical spread) ✓
• D Cerebellum → brainstem → hippocampus

Explanation

Braak and Braak staging of Alzheimer disease describes the progressive spread of neurofibrillary tangles from the transentorhinal cortex (stages I-II), to hippocampus and limbic regions (stages III-IV), and finally to widespread neocortex (stages V-VI). This anatomical progression correlates with clinical severity; early stages (I-II) may be asymptomatic, while stages V-VI correspond to severe dementia.

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

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