{"doi":"10.1002/alz.70637","title":"White matter microstructure is differentially impacted by cerebral amyloid angiopathy, neurofibrillary tangles, and neuritic plaque co‐pathology","abstract":"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.","journal":"Alzheimer s & Dementia","year":2025,"id":527174,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8949,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":907402,"name":"Francisco Almeida","orcid":"0000-0002-8404-4136","position":1,"is_corresponding":false},{"id":470514,"name":"Kathryn Gauthreaux","orcid":null,"position":2,"is_corresponding":false},{"id":42820,"name":"Charles Mock","orcid":"0000-0002-0564-568X","position":3,"is_corresponding":false},{"id":253925,"name":"Walter A. Kukull","orcid":"0000-0001-8761-9014","position":4,"is_corresponding":false},{"id":308308,"name":"John F. Crary","orcid":"0000-0002-0556-293X","position":5,"is_corresponding":false},{"id":378556,"name":"Tiago Gil Oliveira","orcid":"0000-0003-0509-0562","position":6,"is_corresponding":false},{"id":1221968,"name":"Alexandra Santos","orcid":"0000-0002-7381-043X","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:50:39.280101Z","pmid":"41085201","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}