Density profiles of Alzheimer disease regional brain pathology for the Huddinge brain bank: pattern recognition emulates and expands upon Braak staging

Density profiles of Alzheimer's disease (AD) regional brain pathology were constructed for 249 subjects in the Huddinge Brain Bank. Counts: per square millimeter for neurofibrillary tangles (NFT), diffuse plaques (DP), and ne uritic plaques (NP) in 38 areas were investigated using a pattern recogniti on technique called GoM. The seven distributional profiles of AD neuropatho logy emulated and expanded upon Braak staging illustrating induction (Group s 1-3) and clinical progression (Groups 4-7). Normal aging represented limi ted AD changes, few NFT in the entorhinal cortex and hippocampal CA1 (Group 1). The threshold fur possible AD was NFT in the subiculum (Group 2). foun d with DP in the neocortex. Temporal medial NFT was the threshold for proba ble AD (Group 4). The 'oldest-old', often demented without brain atrophy, h ad extensive entorhinal/CA1 NFT and cortical DP, but few cortical NFT or NP (Group 5). A second subtype 'disconnection' (Group 6) lacked AD pathology for a specific set of subcortical and cortical areas. Accumulation of NFT i n first-affected areas continued through end-stage disease (Group 7), with apparent rapid transition of DP to NP in the cortex during clinical progres sion. The evolution of AD is a highly ordered sequential process. Pattern r ecognition approaches such as GoM may be useful in better defining the proc ess. (C) 2000 Elsevier Science Inc. All rights reserved.