{"doi":"10.1002/alz.70254","title":"Arteriolar degeneration and stiffness in cerebral amyloid angiopathy are linked to Aβ deposition and lysyl oxidase","abstract":"INTRODUCTION: The morphological and molecular changes associated with the degeneration of arterioles in cerebral amyloid angiopathy (CAA) are incompletely understood. METHODS: Post mortem brains from 26 patients with CAA or neurological controls were analyzed using light-sheet microscopy, and morphological features of microvascular degeneration were quantified using surface volume rendering. Vascular stiffness was analyzed using atomic force microscopy. RESULT: Vascular smooth muscle cells (VSMCs) volume was reduced by ≈ 55% in CAA. This loss of VSMC volume correlated with increased arteriolar diameter, variability in diameter, and the volume of amyloid beta (Aβ) deposition in the vessel. Vessels with CAA were > 300% stiffer than controls. The volume of extracellular matrix cross-linking enzyme lysyl oxidase (LOX) correlated closely with vascular degenerative features. DISCUSSION: Our findings provide valuable insights into the connections among LOX, Aβ deposition, and vascular stiffness in CAA. Restoration of physiologic extracellular matrix properties in penetrating arteries may yield a novel therapeutic strategy for CAA. HIGHLIGHTS: We conducted 3D microscopy on human brains with cerebral amyloid angiopathy. We quantified features of vascular degeneration, β-amyloid, and lysyl oxidase in CAA Vascular degeneration correlated with Aβ, loss of VSMCs , and increased LOX. Arterioles with CAA were stiffer than controls in data from atomic force microscopy. Vascular extracellular matrix properties may be a therapeutic target for CAA.","journal":"Alzheimer s & Dementia","year":2025,"id":511846,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9564,"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":1329471,"name":"Alex Nackenoff","orcid":"0000-0002-6763-1953","position":1,"is_corresponding":false},{"id":805586,"name":"Wilber Romero‐Fernandez","orcid":"0000-0001-9868-8074","position":2,"is_corresponding":false},{"id":500938,"name":"Yongchao Wang","orcid":"0000-0001-9560-682X","position":3,"is_corresponding":false},{"id":714939,"name":"Allison M. Bosworth","orcid":null,"position":4,"is_corresponding":false},{"id":1086794,"name":"Alex Prusky","orcid":"0009-0009-3089-4600","position":5,"is_corresponding":false},{"id":1018849,"name":"Emmeline Wang","orcid":null,"position":6,"is_corresponding":false},{"id":1086793,"name":"Cristian Carvajal‐Tapia","orcid":"0000-0002-5590-6905","position":7,"is_corresponding":false},{"id":346175,"name":"Alena Shostak","orcid":null,"position":8,"is_corresponding":false},{"id":905847,"name":"Hannah Harmsen","orcid":"0000-0003-2634-0321","position":9,"is_corresponding":false},{"id":480935,"name":"Bret C. Mobley","orcid":"0000-0002-8138-5330","position":10,"is_corresponding":false},{"id":651298,"name":"J. Maldonado","orcid":"0000-0002-8008-7059","position":11,"is_corresponding":false},{"id":1371229,"name":"Neely Womble","orcid":null,"position":12,"is_corresponding":false},{"id":1017741,"name":"Elena Solopova","orcid":"0000-0001-5508-0368","position":13,"is_corresponding":false},{"id":1077715,"name":"J. Caleb Snider","orcid":"0000-0003-3568-381X","position":14,"is_corresponding":false},{"id":321482,"name":"W. David Merryman","orcid":"0000-0001-9662-1503","position":15,"is_corresponding":false},{"id":331785,"name":"Ethan S. Lippmann","orcid":"0000-0001-5703-5747","position":16,"is_corresponding":false},{"id":353780,"name":"Matthew Schrag","orcid":"0000-0001-7048-0503","position":17,"is_corresponding":false},{"id":1017742,"name":"Lissa Ventura‐Antunes","orcid":"0000-0001-5508-0990","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T02:48:01.269605Z","pmid":"40465757","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":[]}