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, the ADGC Neuropathology Core Leaders Subcommittee derived inclusion and exclusion criteria for AD and control samples. All autopsied subjects were age ≥ 60 years at death. AD cases were demented according to DSM-IV criteria or Clinical Dementia Rating (CDR) ≥1. Neuropathologic stratification of cases followed NIA/Reagan criteria explicitly, or used a similar approach when NIA/Reagan criteria were coded as not done, missing, or unknown. Cases were intermediate or high likelihood by NIA/Reagan criteria with moderate to frequent amyloid plaques and neurofibrillary tangle (NFT) Braak stage of III-VI. Persons with Down syndrome, non-AD tauopathies and synucleinopathies were excluded. All autopsied controls had a clinical evaluation within two years of death.
Controls did not meet DSM-IV criteria for dementia, did not have a diagnosis of mild cognitive impairment (MCI), and had a CDR of 0, if performed. Controls did not meet or were low-likelihood AD by NIA/Reagan criteria, had sparse or no amyloid plaques, and a Braak NFT stage of 0 – II. 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 sent to the genotyping site at Children’s Hospital of Philadelphia. ADRC samples were genotyped and analyzed in separate batches.