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F4‐03‐02: NEUROPATHOLOGICAL SUBSTRATE OF IMAGING BIOMARKERS ‐ VALIDATING NEUROIMAGING BIOMARKERS IN AD USING HIGH‐RESOLUTION 3D HISTOLOGICAL MAPPING
Author(s) -
Alegro Maryana,
Heinsen Helmut,
Amaro Edson,
Eser Rana,
Morales Dulce,
Chen Yuheng,
Ushizima Daniela,
Tosun Duygu,
Grinberg Lea T.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.4723
Subject(s) - neuroimaging , voxel , computer science , artificial intelligence , neuroscience , pathology , medicine , psychology
basal forebrain atrophy as determined using antemortem MRI and comprehensive post-mortem assessment of global and local neuropathologic features, including neuritic plaques, neurofibrillary tangles (NFT), alpha-synuclein, and TDP-43, in 64 cases of the ADNI cohort. For comparison, we determined neuropathological features of medial temporal lobe atrophy (MTL), including hippocampus and parahippocampal gyrus. We used region of interest as well as regionally unbiased voxel based regression analyses. Results: Thal neuritic and diffuse amyloid plaque phases and alpha-synuclein but not local NFT pathology were significant predictors for basal forebrain atrophy (Figure 1), whereas neuronal loss, NFT and TDP-43 load were major predictors of MTL atrophy (Figure 2). Conclusions: These findings suggest that cholinergic basal forebrain atrophy within the AD spectrum is mainly driven by amyloid pathology in remote cortical input areas of cholinergic projections and by local and remote alpha-synuclein pathology. The regional variation in the underlying neuropathological features of local brain atrophy underscores the need for comprehensive assessment of underlying pathologies for the future design of individualized treatments.