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FHS participants volunteered to donate their brains for research purposes upon their demise. Upon receiving the notification of a donor’s death, the FHS-BAP team will contact the designated next-of-kin to initiate the process.

Neuropathological evaluation of all autopsied brains is performed by neuropathologists blinded to all demographic and clinical information. Briefly, brains are usually received fresh, and the gross neuropathological findings are recorded, including measurement and documentation of all grossly visible vascular lesions and the degree of atherosclerosis in the circle of Willis.

Neuropathological criteria

Neuropathological criteria for the diagnosis of AD/ADRD and other neurodegenerations are used as developed by the NIA-AA Working Group; criteria for CTE follow the recommendations of the NINDS consensus panel. The criteria for AD are based on the presence of amyloid-neuritic plaques and p-tau neurofibrillary tangles according to the NIA–Reagan criteria for intermediate and high likelihood Alzheimer’s disease and the recent NIA Alzheimer Association’s guidelines. The NIA–Reagan criteria consider both the Braak staging of neurofibrillary tangles and the overall density of neuritic plaques based on CERAD criteria. The diagnosis of Lewy body disease is based on the presence and distribution of alpha-synuclein-positive Lewy bodies and is considered brainstem-predominant, limbic or transitional Lewy body disease, and neocortical or diffuse Lewy body disease as defined by McKeith criteria and Braak staging.

Neuropathology protocol