Braak · Neurobiology of aging 2003 · Post-mortem neuropathological case series · n=?

Staging of brain pathology related to sporadic Parkinson's disease.

Cited 10898 times in the scientific literature.

Level 4 - case-series / case-control

Post-mortem neuropathological case series proposing a pathological staging scheme.

PubMed 12498954 · doi:10.1016/s0197-4580(02)00065-9 · record verified 2026-08-27

What was done

The authors analyzed post-mortem brain tissue from incidental and symptomatic sporadic Parkinson's disease cases using alpha-synuclein immunohistochemistry (identifying Lewy bodies and Lewy neurites) to trace the anatomical distribution of pathology and develop a neuropathological staging system.

What was found

The abstract reports no numerical data or case counts. Qualitatively, pathology initially appears in the dorsal motor nucleus of the glossopharyngeal and vagal nerves as well as the anterior olfactory nucleus. The disease follows an ascending brainstem trajectory with minimal interindividual variation, subsequently advancing into the anteromedial temporal mesocortex, high-order sensory association and prefrontal neocortical regions, and finally first-order sensory association, premotor, and primary sensory/motor cortices.

Why it matters

This study introduced the Braak staging model of sporadic Parkinson's disease, proposing that alpha-synuclein pathology progresses along a stereotypical anatomical pathway starting outside the substantia nigra in the lower brainstem and olfactory structures before ascending to the cerebral cortex.

Limits

The abstract does not disclose the sample size, patient demographics, clinical characteristics, or any quantitative metrics. In addition, the chronological staging model is inferred from cross-sectional post-mortem evaluations rather than direct longitudinal observation.

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