The NIA ADRC cohort included subjects ascertained and evaluated by the clinical and neuropathology cores of the 32 NIA-funded ADRCs. Data collection is coordinated by the National Alzheimer’s Coordinating Center (NACC). NACC coordinates collection of phenotype data from the 32 ADRCs, cleans all data, coordinates implementation of definitions of AD cases and controls, and coordinates collection of samples. The ADRC cohort consists of autopsy-confirmed and clinically-confirmed AD cases, and cognitively normal elders (CNEs) with complete neuropathology data who were older than 60 years at age of death, and living CNEs evaluated using the Uniform dataset (UDS) protocol who were documented to not have mild cognitive impairment (MCI) and were between 60 and 100 years of age at assessment.

Based on the data collected by NACC, ADSP Phenotype Harmonization Consortium (ADSP-PHC) derived inclusion and exclusion criteria for AD and control samples. Clinical AD cases were demented according to NACC’s cognitive status of dementia at UDS visit with a primary etiologic diagnosis of Alzheimer’s Dementia. Controls did not meet dementia or MCI criteria and exhibited no etiologic diagnoses. Neuropathologic definition of cases and control followed NIA-AA Alzheimer’s disease neuropathologic change (ADNC) scores (ABC method), with intermediate or higher ADNC scores classified as Cases and low ADNC scores labeled Controls. When ADNC scores were not available, a similar approach was used with BRAAK and CERAD scores, with Cases possessing a BRAAK Stage greater than or equal to III and a CERAD score of either moderate or frequent neuritic plaques. Consistent with the ADNC definition, if a participant was lower on BRAAK or CERAD they were given a Control diagnosis (equivalent to a low score on ADNC). Individuals missing an ADNC score and either BRAAK or CERAD score were not given a neuropathologic diagnosis. Persons with Down’s syndrome, neuropsychiatric, neurodegenerative, and neurologic disorders, brain structure abnormalities, non-AD tauopathies and synucleinopathies were excluded from both clinical and autopsy diagnoses of cases and controls. All autopsied controls had a clinical evaluation within two years of death. An autopsy-confirmed variable was derived from matching neuropath and clinical diagnoses when available. All cases and controls were required to be >60 years of age.

ADRCs sent frozen tissue from autopsied subjects and DNA samples from some autopsied subjects and from living subjects to the ADRCs to the National Cell Repository for Alzheimer’s Disease (NCRAD). DNA was prepared by NCRAD for genotyping and sequencing.