Neuropathological diagnostic criteria for Alzheimer's disease

Neuropathological diagnostic criteria for Alzheimer's disease (AD) are based on tau-related pathology: NFT or neuritic plaques (NP). The Consortium to Establish a Registry for Alzheimer's disease (CERAD) criterion evaluates the highest density of neocortical NP from 0 (none) to C (abundant). Clinical documentation of dementia and NP stage A in younger cases, B in young old cases and C in older cases fulfils the criterion of AD. The CERAD criterion is most frequently used in clinical outcome studies because of its inclusion of clinical information. Braak and Braak's criterion evaluates the density and distribution of NFT and classifies them into: I/II, entorhinal; III/IV, limbic; and V/VI, neocortical stage. These three stages correspond to normal cognition, cognitive impairment and dementia, respectively. As Braak's criterion is based on morphological evaluation of the brain alone, this criterion is usually adopted in the research setting. The National Institute for Aging and Ronald and Nancy Reagan Institute of the Alzheimer's Association criterion combines these two criteria and categorizes cases into NFT V/VI and NP C, NFT III/IV and NP B, and NFT I/II and NP A, corresponding to high, middle and low probability of AD, respectively. As most AD cases in the aged population are categorized into Braak tangle stage IV and CERAD stage C, the usefulness of this criterion has not yet been determined. The combination of Braak's NFT stage equal to or above IV and Braak's senile plaque Stage C provides, arguably, the highest sensitivity and specificity. In future, the criteria should include in vivo dynamic neuropathological data, including 3D MRI, PET scan and CSF biomarkers, as well as more sensitive and specific immunohistochemical and immunochemical grading of AD.