Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
White matter microstructure is differentially impacted by cerebral amyloid angiopathy, neurofibrillary tangles, and neuritic plaque co-pathology.
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Santos Alexandra, Almeida Francisco C, Gauthreaux Kathryn, Mock Charles N, Kukull Walter A, Crary John F, Oliveira Tiago Gil
Аннотация
INTRODUCTION: White matter (WM) is affected by and serves as a pathway to neurofibrillary tangle (NFT) propagation in Alzheimer's disease (AD). Cerebral amyloid angiopathy (CAA) associates with neuritic plaques (NPs) to exacerbate NFT accumulation. We aim to study how these co-pathologies affect WM integrity.
METHODS: We performed a cross-sectional study of ante mortem diffusion tensor imaging (DTI) data according to participants' post mortem NFT, NP, and CAA neuropathology, from the National Alzheimer's Coordinating Center dataset.
RESULTS: We found asymmetric DTI changes in several WM regions between Braak NFT stages II and IV and V/VI, and across CAA pathological burden, with increased mean, radial, and axial diffusivities. CAA-NFT co-pathology effects were observed mainly in the splenium of the corpus callosum. DTI metrics were associated with cognitive function and hippocampal volumes.
DISCUSSION: Our results suggest that WM integrity is differentially impacted by AD neuropathology, with CAA and NFTs influencing each other's effects on WM microstructure.
HIGHLIGHTS: Diffusion tensor imaging (DTI) changes were observed in several white matter (WM) regions between advanced Braak stages and across cerebral amyloid angiopathy (CAA). CAA demonstrated a greater WM impact on the right hemisphere, while neurofibrillary tangles (NFTs) had greater impact on the left. CAA-NFT concurrent effects were mainly noticed in the splenium of the corpus callosum. WM DTI metrics were associated with cognition and hippocampal volumes.
METHODS: We performed a cross-sectional study of ante mortem diffusion tensor imaging (DTI) data according to participants' post mortem NFT, NP, and CAA neuropathology, from the National Alzheimer's Coordinating Center dataset.
RESULTS: We found asymmetric DTI changes in several WM regions between Braak NFT stages II and IV and V/VI, and across CAA pathological burden, with increased mean, radial, and axial diffusivities. CAA-NFT co-pathology effects were observed mainly in the splenium of the corpus callosum. DTI metrics were associated with cognitive function and hippocampal volumes.
DISCUSSION: Our results suggest that WM integrity is differentially impacted by AD neuropathology, with CAA and NFTs influencing each other's effects on WM microstructure.
HIGHLIGHTS: Diffusion tensor imaging (DTI) changes were observed in several white matter (WM) regions between advanced Braak stages and across cerebral amyloid angiopathy (CAA). CAA demonstrated a greater WM impact on the right hemisphere, while neurofibrillary tangles (NFTs) had greater impact on the left. CAA-NFT concurrent effects were mainly noticed in the splenium of the corpus callosum. WM DTI metrics were associated with cognition and hippocampal volumes.