{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:57:42Z","timestamp":1785434262102,"version":"3.56.0"},"posted":{"date-parts":[[2025,12,11]]},"group-title":"Neuroscience","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01 AG081932"],"award-info":[{"award-number":["R01 AG081932"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P41 EB031771"],"award-info":[{"award-number":["P41 EB031771"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Cerebral microbleeds are increasingly recognized as a downstream manifestation of vascular injury in Alzheimer\u2019s disease (AD), arising secondary to cerebral amyloid angiopathy (CAA). Here, we examined the pathological specificity of microbleeds by comparing an amyloidosis mouse model (5xFAD) with a small-vessel disease (SVD) model characterized by vascular smooth-muscle cell loss.\n                  <jats:italic>In vivo<\/jats:italic>\n                  multimodal MRI, including gradient-echo, spin-echo, and diffusion-weighted imaging, was complemented by\n                  <jats:italic>ex vivo<\/jats:italic>\n                  high-resolution anatomical scans for validation. Both\n                  <jats:italic>in vivo<\/jats:italic>\n                  and\n                  <jats:italic>ex vivo<\/jats:italic>\n                  gradient-echo MRI consistently revealed hippocampal microbleeds in the 5xFAD model without macroscopic atrophy or ventricular enlargement, whereas no microbleeds or blood-brain barrier disruption were detected in the SVD model. Diffusion-weighted MRI further showed region-specific alterations in apparent diffusion coefficient within the midbrain of 5xFAD mice, but not in other regions or in the SVD cohort. These findings indicate that microbleeds are a pathology-specific marker of amyloid-related vascular injury. The imaging evidence underscores the potential of microbleeds as a disease-specific biomarker for detecting amyloid-driven vascular fragility and refining diagnostic and therapeutic strategies for AD.\n                <\/jats:p>","DOI":"10.64898\/2025.12.08.692809","type":"posted-content","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T16:20:11Z","timestamp":1765470011000},"source":"Crossref","is-referenced-by-count":1,"title":["Vascular Microbleeds Without Brain Atrophy: A Microvascular Signature of Mid-Stage 5xFAD Pathology"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8277-4285","authenticated-orcid":false,"given":"Xiuli","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuguo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8044-2906","authenticated-orcid":false,"given":"Adnan","family":"Bibic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1896-9552","authenticated-orcid":false,"given":"Jiekang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9404-540X","authenticated-orcid":false,"given":"Mei","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5933-6308","authenticated-orcid":false,"given":"Wenzhen","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3871-1564","authenticated-orcid":false,"given":"Hanzhang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8477-2440","authenticated-orcid":false,"given":"Zhiliang","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025121500350734000_2025.12.08.692809v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70013-4"},{"key":"2025121500350734000_2025.12.08.692809v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-83607-0"},{"key":"2025121500350734000_2025.12.08.692809v1.3","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq321"},{"key":"2025121500350734000_2025.12.08.692809v1.4","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22516"},{"key":"2025121500350734000_2025.12.08.692809v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2012.07.009"},{"key":"2025121500350734000_2025.12.08.692809v1.6","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt263"},{"key":"2025121500350734000_2025.12.08.692809v1.7","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22099"},{"key":"2025121500350734000_2025.12.08.692809v1.8","doi-asserted-by":"crossref","first-page":"3328","DOI":"10.1002\/acn3.52226","article-title":"Distinct neuroinflammatory patterns between cerebral microbleeds and microinfarcts in cerebral amyloid angiopathy","volume":"11","year":"2024","journal-title":"Ann Clin Transl Neurol"},{"key":"2025121500350734000_2025.12.08.692809v1.9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3389\/fnagi.2020.00013","article-title":"Increased presence of cerebral microbleeds correlates with ventricular enlargement and increased white matter hyperintensities in Alzheimer\u2019s disease","volume":"12","year":"2020","journal-title":"Front Aging Neurosci"},{"key":"2025121500350734000_2025.12.08.692809v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2021.105905"},{"key":"2025121500350734000_2025.12.08.692809v1.11","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1161\/STROKEAHA.124.048974","article-title":"Cerebral microbleeds and their association with inflammation and blood-brain barrier leakage in small vessel disease","volume":"56","year":"2025","journal-title":"Stroke"},{"key":"2025121500350734000_2025.12.08.692809v1.12","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-014-0206-2"},{"key":"2025121500350734000_2025.12.08.692809v1.13","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.123.19943"},{"key":"2025121500350734000_2025.12.08.692809v1.14","first-page":"e452","article-title":"Management of inherited CNS small vessel diseases: The CADASIL example: a scientific statement from the American Heart Association","volume":"54","year":"2023","journal-title":"Stroke"},{"key":"2025121500350734000_2025.12.08.692809v1.15","doi-asserted-by":"crossref","unstructured":"Braun DJ , Abner E , Bakshi V et al. 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