{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:06:33Z","timestamp":1789549593025,"version":"build-2803163510"},"reference-count":108,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) involves not only the neural parenchyma but also brain-border interfaces in which border-associated macrophages (BAMs) regulate amyloid-\u03b2 (A\u03b2) handling, vascular function, and immune surveillance. This review focuses on a pathological axis in which persistent vascular A\u03b240 and aging-related stress shift clearance-competent BAMs toward oxidative-stress and senescent-like states. Two experimentally supported but incompletely connected branches are emphasized. In one, A\u03b2 engages macrophage CD36\u2013NOX2 signaling and generates reactive oxygen species that impair neurovascular function. In the other, A\u03b240 internalization promotes TSPAN4-dependent migrasome formation and enrichment of CD5L\/AIM; vascularly deposited CD5L\/AIM lowers endothelial CD59, facilitates C5b\u20139 formation, and damages the blood\u2013brain barrier. A separate aging study indicates that CD5L\/AIM-rich BAM migrasomes can transmit apoptosis resistance and senescence-like dysfunction to microglia. Human evidence is currently strongest for CAA rather than parenchymal AD: a small CAA cohort showed increased circulating CD14-positive migrasomes and monocyte TSPAN4, with an exploratory area under the ROC curve of approximately 0.91 for TSPAN4-positive monocytes versus healthy controls, whereas AD patients selected to lack imaging evidence of CAA did not show increased circulating migrasome counts. Accordingly, the A\u03b240\u2013TSPAN4\u2013CD5L\/AIM vascular branch should presently be regarded as a CAA-enriched mechanism that may be especially relevant to AD with prominent CAA, not as a universal mechanism of A\u03b242-dominant sporadic AD without substantial vascular amyloid. Direct demonstration of BAM-derived migrasomes in human AD brain tissue is still lacking, and neither TSPAN4 nor CD5L\/AIM is sufficiently specific to serve as a stand-alone biomarker. We therefore distinguish peer-reviewed human observations, experimental causal evidence, preprint findings, and proposed cross-pathway interactions and outline biomarker validation and pathway-selective therapeutic strategies that preserve beneficial BAM functions.<\/jats:p>","DOI":"10.3390\/cells15181671","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:58:59Z","timestamp":1789545539000},"page":"1671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Border-Associated Macrophage Migrasomes in Alzheimer\u2019s Disease: An Emerging A\u03b2\u2013Senescence\u2013Microglia Axis?"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5320-3658","authenticated-orcid":false,"given":"James","family":"Chmiel","sequence":"first","affiliation":[{"name":"Institute of Physical Culture Sciences, Faculty of Physical Culture and Health, University of Szczecin, Al. Piast\u00f3w 40B Block 6, 71-065 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3936-0698","authenticated-orcid":false,"given":"Marta","family":"Kopa\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Medical Communication and Professional Competency Development, Faculty of Medicine, Collegium Medicum, University of Rzesz\u00f3w, 35-310 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature14432","article-title":"Structural and functional features of central nervous system lymphatic vessels","volume":"523","author":"Louveau","year":"2015","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1084\/jem.20142290","article-title":"A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules","volume":"212","author":"Aspelund","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.cell.2020.12.040","article-title":"Functional characterization of the dural sinuses as a neuroimmune interface","volume":"184","author":"Rustenhoven","year":"2021","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1038\/s41593-019-0393-4","article-title":"A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment","volume":"22","author":"Martens","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.1016\/j.cell.2021.04.003","article-title":"A cellular and spatial map of the choroid plexus across brain ventricles and ages","volume":"184","author":"Dani","year":"2021","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7036","DOI":"10.1038\/s41467-023-42825-y","article-title":"Dissecting the human leptomeninges at single-cell resolution","volume":"14","author":"Kearns","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"147ra111","DOI":"10.1126\/scitranslmed.3003748","article-title":"A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid \u03b2","volume":"4","author":"Iliff","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1126\/science.1241224","article-title":"Sleep drives metabolite clearance from the adult brain","volume":"342","author":"Xie","year":"2013","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1002\/ana.24271","article-title":"Impairment of paravascular clearance pathways in the aging brain","volume":"76","author":"Kress","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3897","DOI":"10.1038\/s41467-022-31257-9","article-title":"Periarteriolar spaces modulate cerebrospinal fluid transport into brain and demonstrate altered morphology in aging and Alzheimer\u2019s disease","volume":"13","author":"Mestre","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41586-022-05397-3","article-title":"Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid","volume":"611","author":"Drieu","year":"2022","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.neuron.2014.12.032","article-title":"Blood-brain barrier breakdown in the aging human hippocampus","volume":"85","author":"Montagne","year":"2015","journal-title":"Neuron"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","article-title":"Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction","volume":"25","author":"Nation","year":"2019","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/nature11087","article-title":"Apolipoprotein E controls cerebrovascular integrity via cyclophilin A","volume":"485","author":"Bell","year":"2012","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41586-020-2247-3","article-title":"APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline","volume":"581","author":"Montagne","year":"2020","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4758","DOI":"10.1038\/s41467-024-48926-6","article-title":"Gliovascular transcriptional perturbations in Alzheimer\u2019s disease reveal molecular mechanisms of blood brain barrier dysfunction","volume":"15","author":"Wang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1038\/s41593-024-01757-6","article-title":"A cell-autonomous role for border-associated macrophages in ApoE4 neurovascular dysfunction and susceptibility to white matter injury","volume":"27","author":"Anfray","year":"2024","journal-title":"Nat. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41586-018-0368-8","article-title":"Functional aspects of meningeal lymphatics in ageing and Alzheimer\u2019s disease","volume":"560","author":"Louveau","year":"2018","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41586-021-03489-0","article-title":"Meningeal lymphatics affect microglia responses and anti-A\u03b2 immunotherapy","volume":"593","author":"Papadopoulos","year":"2021","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1177\/153537020523001011","article-title":"The choroid plexus removes beta-amyloid from brain cerebrospinal fluid","volume":"230","author":"Crossgrove","year":"2005","journal-title":"Exp. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Marrero, I., Gim\u00e9nez-Llort, L., Johanson, C.E., Carmona-Calero, E.M., Casta\u00f1eyra-Ruiz, L., Brito-Armas, J.M., Casta\u00f1eyra-Perdomo, A., and Castro-Fuentes, R. (2015). Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic mouse model of Alzheimer\u2019s disease. Front. Cell. Neurosci., 9.","DOI":"10.3389\/fncel.2015.00017"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1038\/s41593-018-0213-2","article-title":"Direct vascular channels connect skull bone marrow and the brain surface enabling myeloid cell migration","volume":"21","author":"Herisson","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"eabf7844","DOI":"10.1126\/science.abf7844","article-title":"Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma","volume":"373","author":"Cugurra","year":"2021","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41593-022-01029-1","article-title":"Cerebrospinal fluid regulates skull bone marrow niches via direct access through dural channels","volume":"25","author":"Mazzitelli","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/s41593-022-01060-2","article-title":"Cerebrospinal fluid can exit into the skull bone marrow and instruct cranial hematopoiesis in mice with bacterial meningitis","volume":"25","author":"Pulous","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1073\/pnas.0805453106","article-title":"Selective targeting of perivascular macrophages for clearance of beta-amyloid in cerebral amyloid angiopathy","volume":"106","author":"Hawkes","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1161\/CIRCRESAHA.117.311054","article-title":"Brain Perivascular Macrophages Initiate the Neurovascular Dysfunction of Alzheimer A\u03b2 Peptides","volume":"121","author":"Park","year":"2017","journal-title":"Circ. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13024-023-00660-1","article-title":"Border-associated macrophages promote cerebral amyloid angiopathy and cognitive impairment through vascular oxidative stress","volume":"18","author":"Uekawa","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13024-023-00649-w","article-title":"Amyloid-\u03b2 (A\u03b2) immunotherapy induced microhemorrhages are associated with activated perivascular macrophages and peripheral monocyte recruitment in Alzheimer\u2019s disease mice","volume":"18","author":"Taylor","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1038\/s41593-026-02267-3","article-title":"Spatial proteomic analysis in human Alzheimer\u2019s disease brains enables identification of microenvironment-dependent microglial cell states","volume":"29","author":"Rosmus","year":"2026","journal-title":"Nat. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/ni.3423","article-title":"Origin, fate and dynamics of macrophages at central nervous system interfaces","volume":"17","author":"Goldmann","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.cell.2020.03.021","article-title":"Early Fate Defines Microglia and Non-parenchymal Brain Macrophage Development","volume":"181","author":"Utz","year":"2020","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.immuni.2020.11.007","article-title":"A Binary Cre Transgenic Approach Dissects Microglia and CNS Border-Associated Macrophages","volume":"54","author":"Kim","year":"2021","journal-title":"Immunity"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/s41586-022-04596-2","article-title":"Specification of CNS macrophage subsets occurs postnatally in defined niches","volume":"604","author":"Masuda","year":"2022","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/s41591-023-02673-1","article-title":"Multiomic spatial landscape of innate immune cells at human central nervous system borders","volume":"30","author":"Sankowski","year":"2024","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7366","DOI":"10.1038\/s41467-022-35166-9","article-title":"Deciphering the heterogeneity of the Lyve1+ perivascular macrophages in the mouse brain","volume":"13","author":"Siret","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.immuni.2023.01.028","article-title":"A Cre-deleter specific for embryo-derived brain macrophages reveals distinct features of microglia and border macrophages","volume":"56","author":"Brioschi","year":"2023","journal-title":"Immunity"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1016\/j.immuni.2022.09.005","article-title":"Differential plasticity and fate of brain-resident and recruited macrophages during the onset and resolution of neuroinflammation","volume":"55","author":"Kancheva","year":"2022","journal-title":"Immunity"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"114120","DOI":"10.1016\/j.celrep.2024.114120","article-title":"CCR2+ monocytes replenish border-associated macrophages in the diseased mouse brain","volume":"43","author":"Wang","year":"2024","journal-title":"Cell Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Adler, D., Pinheiro-Rosa, N., Millet, A., Gajic, Z.Z., Cheng, E., Gamallo-Lana, B., Morizawa, Y., Klann, E., Gan, W.B., and Mar, A.C. (2026). Functional border-associated macrophages limit Alzheimer\u2019s Disease progression. bioRxiv.","DOI":"10.64898\/2026.01.31.703045"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1016\/j.ajpath.2025.05.017","article-title":"Distinct Role of Dural and Leptomeningeal Macrophages in Maintaining Cerebrospinal Fluid Drainage to Meningeal Lymphatic Vessels","volume":"195","author":"Lohat","year":"2025","journal-title":"Am. J. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/cr.2014.135","article-title":"Discovery of the migrasome, an organelle mediating release of cytoplasmic contents during cell migration","volume":"25","author":"Ma","year":"2015","journal-title":"Cell Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1038\/cr.2017.108","article-title":"Pairing of integrins with ECM proteins determines migrasome formation","volume":"27","author":"Wu","year":"2017","journal-title":"Cell Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e202109168","DOI":"10.1083\/jcb.202109168","article-title":"Cell migration orchestrates migrasome formation by shaping retraction fibers","volume":"221","author":"Fan","year":"2022","journal-title":"J. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/s41556-019-0367-5","article-title":"Migrasome formation is mediated by assembly of micron-scale tetraspanin macrodomains","volume":"21","author":"Huang","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/s41420-023-01673-x","article-title":"Migrasome: A new functional extracellular vesicle","volume":"9","author":"Zhang","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41421-019-0093-y","article-title":"Identification of markers for migrasome detection","volume":"5","author":"Zhao","year":"2019","journal-title":"Cell Discov."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41421-024-00729-1","article-title":"Bacterial toxins induce non-canonical migracytosis to aggravate acute inflammation","volume":"10","author":"Li","year":"2024","journal-title":"Cell Discov."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/s41422-023-00811-5","article-title":"The phosphatidylinositol (4,5)-bisphosphate-Rab35 axis regulates migrasome formation","volume":"33","author":"Ding","year":"2023","journal-title":"Cell Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1038\/s41467-023-36596-9","article-title":"Tetraspanin 4 stabilizes membrane swellings and facilitates their maturation into migrasomes","volume":"14","author":"Dharan","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/s41556-023-01188-8","article-title":"The formation of migrasomes is initiated by the assembly of sphingomyelin synthase 2 foci at the leading edge of migrating cells","volume":"25","author":"Liang","year":"2023","journal-title":"Nat. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e202402060","DOI":"10.1083\/jcb.202402060","article-title":"Calcium ions promote migrasome formation via Synaptotagmin-1","volume":"223","author":"Han","year":"2024","journal-title":"J. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7162","DOI":"10.1038\/s41467-026-73674-0","article-title":"GPI-anchored protein nanoclusters license migrasome expansion and serve as exocytic platforms for migrasome","volume":"17","author":"Li","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/s41422-020-00415-3","article-title":"Lateral transfer of mRNA and protein by migrasomes modifies the recipient cells","volume":"31","author":"Zhu","year":"2021","journal-title":"Cell Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e2319267121","DOI":"10.1073\/pnas.2319267121","article-title":"Rab10-CAV1 mediated intraluminal vesicle transport to migrasomes","volume":"121","author":"Li","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/s41422-024-00992-7","article-title":"Localized, highly efficient secretion of signaling proteins by migrasomes","volume":"34","author":"Jiao","year":"2024","journal-title":"Cell Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.1038\/s41467-023-39693-x","article-title":"Macrophage lineage cells-derived migrasomes activate complement-dependent blood-brain barrier damage in cerebral amyloid angiopathy mouse model","volume":"14","author":"Hu","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/s41556-019-0358-6","article-title":"Migrasomes provide regional cues for organ morphogenesis during zebrafish gastrulation","volume":"21","author":"Jiang","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1038\/s41556-022-01026-3","article-title":"Monocytes deposit migrasomes to promote embryonic angiogenesis","volume":"24","author":"Zhang","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5022","DOI":"10.1038\/s41467-026-71616-4","article-title":"PGC-derived migrasomes couple PGC proliferation with migration","volume":"17","author":"Liu","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2896","DOI":"10.1016\/j.cell.2021.04.027","article-title":"Mitocytosis, a migrasome-mediated mitochondrial quality-control process","volume":"184","author":"Jiao","year":"2021","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/s41556-024-01440-9","article-title":"Neutrophil-derived migrasomes are an essential part of the coagulation system","volume":"26","author":"Jiang","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Schmidt-Pogoda, A., Strecker, J.K., Liebmann, M., Massoth, C., Beuker, C., Hansen, U., K\u00f6nig, S., Albrecht, S., Bock, S., and Breuer, J. (2018). Dietary salt promotes ischemic brain injury and is associated with parenchymal migrasome formation. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0209871"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1038\/s43587-025-00956-5","article-title":"Senescent-like border-associated macrophages regulate cognitive aging via migrasome-mediated induction of paracrine senescence in microglia","volume":"5","author":"Hu","year":"2025","journal-title":"Nat. Aging"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/j.1365-2990.2007.00926.x","article-title":"Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: Significance for cerebral amyloid angiopathy and neuroimmunology","volume":"34","author":"Carare","year":"2008","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00401-008-0481-0","article-title":"Alzheimer disease macrophages shuttle amyloid-beta from neurons to vessels, contributing to amyloid angiopathy","volume":"117","author":"Zaghi","year":"2009","journal-title":"Acta Neuropathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3089","DOI":"10.1073\/pnas.1300021110","article-title":"Innate immunity receptor CD36 promotes cerebral amyloid angiopathy","volume":"110","author":"Park","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41582-019-0281-2","article-title":"Cerebral amyloid angiopathy and Alzheimer disease\u2014One peptide, two pathways","volume":"16","author":"Greenberg","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7013","DOI":"10.1074\/jbc.270.13.7013","article-title":"Amyloid beta protein (A beta) in Alzheimer\u2019s disease brain. Biochemical and immunocytochemical analysis with antibodies specific for forms ending at A beta 40 or A beta 42(43)","volume":"270","author":"Gravina","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/alz.12366","article-title":"Prevalence of cerebral amyloid angiopathy: A systematic review and meta-analysis","volume":"18","author":"Klijn","year":"2022","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"20816","DOI":"10.1073\/pnas.1005888107","article-title":"Scavenger receptor class B type I regulates perivascular macrophages and modifies amyloid pathology in an Alzheimer mouse model","volume":"107","author":"Thanopoulou","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2445194","DOI":"10.1080\/07853890.2024.2445194","article-title":"Deciphering the role of APOE in cerebral amyloid angiopathy: From genetic insights to therapeutic horizons","volume":"57","author":"Hu","year":"2025","journal-title":"Ann. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e202507023","DOI":"10.1083\/jcb.202507023","article-title":"Palmitoylation of Tspan4 is essential for migrasome formation","volume":"225","author":"Wang","year":"2026","journal-title":"J. Cell Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.cell.2019.10.005","article-title":"Cellular Senescence: Defining a Path Forward","volume":"179","author":"Gorgoulis","year":"2019","journal-title":"Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.18632\/aging.101268","article-title":"p16(Ink4a) and senescence-associated \u03b2-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli","volume":"9","author":"Hall","year":"2017","journal-title":"Aging"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1093\/brain\/awag080","article-title":"Early glymphatic failure in App^NL-F knock-in mice is linked to parenchymal border macrophages loss","volume":"149","author":"Liu","year":"2026","journal-title":"Brain"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13024-024-00758-0","article-title":"Amyloid-\u03b2 (A\u03b2) immunotherapy induced microhemorrhages are linked to vascular inflammation and cerebrovascular damage in a mouse model of Alzheimer\u2019s disease","volume":"19","author":"Taylor","year":"2024","journal-title":"Mol. Neurodegener."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e202302087","DOI":"10.26508\/lsa.202302087","article-title":"Parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration","volume":"6","author":"Drieu","year":"2023","journal-title":"Life Sci. Alliance"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3086010","DOI":"10.1155\/2022\/3086010","article-title":"Alzheimer\u2019s amyloid-\u03b2 accelerates cell senescence and suppresses the SIRT1\/NRF2 pathway in human microglial cells","volume":"2022","author":"An","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s40659-022-00379-1","article-title":"A\u03b2 promotes CD38 expression in senescent microglia in Alzheimer\u2019s disease","volume":"55","author":"Hu","year":"2022","journal-title":"Biol. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1084\/jem.189.2.413","article-title":"Increased susceptibility of thymocytes to apoptosis in mice lacking AIM, a novel murine macrophage-derived soluble factor belonging to the scavenger receptor cysteine-rich domain superfamily","volume":"189","author":"Miyazaki","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.cmet.2005.02.002","article-title":"A role for the apoptosis inhibitory factor AIM\/Sp\u03b1\/Api6 in atherosclerosis development","volume":"1","author":"Arai","year":"2005","journal-title":"Cell Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"109693","DOI":"10.1016\/j.celrep.2021.109693","article-title":"AIM\/CD5L attenuates DAMPs in the injured brain and thereby ameliorates ischemic stroke","volume":"36","author":"Maehara","year":"2021","journal-title":"Cell Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"117468","DOI":"10.1016\/j.celrep.2026.117468","article-title":"CD5L promotes phagocytic removal of amyloid \u03b2 oligomers and improves cognitive function in a mouse model of Alzheimer\u2019s disease","volume":"45","author":"Maehara","year":"2026","journal-title":"Cell Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"8397","DOI":"10.1038\/s41467-024-52175-y","article-title":"CD5L associates with IgM via the J chain","volume":"15","author":"Wang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri2206","article-title":"Fc\u03b3 receptors as regulators of immune responses","volume":"8","author":"Nimmerjahn","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2823","DOI":"10.1182\/blood.V92.8.2823","article-title":"A regulatory role for Fc\u03b3 receptors CD16 and CD32 in the development of murine B cells","volume":"92","author":"Mueller","year":"1998","journal-title":"Blood"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/s41556-023-01158-0","article-title":"Autophagy enables microglia to engage amyloid plaques and prevents microglial senescence","volume":"25","author":"Choi","year":"2023","journal-title":"Nat. Cell Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41586-018-0543-y","article-title":"Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline","volume":"562","author":"Bussian","year":"2018","journal-title":"Nature"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.neuron.2024.11.018","article-title":"A neurodegenerative cellular stress response linked to dark microglia and toxic lipid secretion","volume":"113","author":"Flury","year":"2025","journal-title":"Neuron"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1161\/STROKEAHA.111.627562","article-title":"Amyloid-\u03b2 contributes to blood\u2013brain barrier leakage in transgenic human amyloid precursor protein mice and in humans with cerebral amyloid angiopathy","volume":"43","author":"Hartz","year":"2012","journal-title":"Stroke"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.neurobiolaging.2018.06.004","article-title":"The effects of cerebral amyloid angiopathy on integrity of the blood\u2013brain barrier","volume":"70","author":"Magaki","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1161\/STROKEAHA.118.023788","article-title":"Blood\u2013brain barrier leakage and microvascular lesions in cerebral amyloid angiopathy","volume":"50","author":"Freeze","year":"2019","journal-title":"Stroke"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"fcac245","DOI":"10.1093\/braincomms\/fcac245","article-title":"Blood\u2013brain barrier leakage and perivascular inflammation in cerebral amyloid angiopathy","volume":"4","author":"Kozberg","year":"2022","journal-title":"Brain Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e214336","DOI":"10.1212\/WNL.0000000000214336","article-title":"In vivo imaging of blood\u2013brain barrier leakage using a contrast agent in patients with cerebral amyloid angiopathy: An exploratory study","volume":"105","author":"Kozberg","year":"2025","journal-title":"Neurology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1159\/000486091","article-title":"Complement activation in capillary cerebral amyloid angiopathy","volume":"44","author":"Matsuo","year":"2018","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.nic.2024.12.004","article-title":"Altered Clearance in Alzheimer\u2019s Disease and Cerebral Amyloid Angiopathy","volume":"35","author":"Mohammadi","year":"2025","journal-title":"Neuroimaging Clin. N. Am."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e1716","DOI":"10.1212\/WNL.0000000000200136","article-title":"Cerebrovascular Reactivity Across the Entire Brain in Cerebral Amyloid Angiopathy","volume":"98","author":"Beaudin","year":"2022","journal-title":"Neurology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1177\/13872877261469189","article-title":"Early cerebral amyloid angiopathy-related pathology is associated with localized functional brain connectivity","volume":"11","author":"Drenth","year":"2026","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e71208","DOI":"10.1002\/alz.71208","article-title":"Spatially resolved transcriptomic profiling identifies distinct signatures in parenchymal and vascular microenvironments in Alzheimer\u2019s disease with cerebral amyloid angiopathy","volume":"22","author":"Troncoso","year":"2026","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s00401-009-0615-z","article-title":"Correlation of hypointensities in susceptibility-weighted images to tissue histology in dementia patients with cerebral amyloid angiopathy: A postmortem MRI study","volume":"119","author":"Schrag","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Madangarli, N., Bonsack, F., Dasari, R., and Sukumari-Ramesh, S. (2019). Intracerebral Hemorrhage: Blood Components and Neurotoxicity. Brain Sci., 9.","DOI":"10.3390\/brainsci9110316"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13024-026-00965-x","article-title":"Early binding of anti-amyloid antibodies to CAA drives complement activation, inflammation and ARIA in mice","volume":"21","author":"Bathini","year":"2026","journal-title":"Mol. Neurodegener."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1038\/s41591-025-03574-1","article-title":"Microglial mechanisms drive amyloid-\u03b2 clearance in immunized patients with Alzheimer\u2019s disease","volume":"31","author":"Simonton","year":"2025","journal-title":"Nat. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/s43587-022-00196-x","article-title":"Limited proteolysis\u2013mass spectrometry reveals aging-associated changes in cerebrospinal fluid protein abundances and structures","volume":"2","author":"Shuken","year":"2022","journal-title":"Nat. Aging"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Kang, H., Kim, H., Kim, W.J., French, L., Oh, H., and An, S.S.A. (2026). Vitronectin Modulates Plasma A\u03b2 Oligomerization Propensity Within Altered Albumin Interactome Networks in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27135744"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Strelnikova, P.A., Kononikhin, A.S., Zakharova, N.V., Bugrova, A.E., Indeykina, M.I., Fedorova, Y.B., Kolykhalov, I.V., Morozova, A.Y., Andryushchenko, A.V., and Fedoseeva, E.D. (2026). Plasma Protein Panel for Assessing the Risk of Alzheimer\u2019s Disease by MRM-MS Analysis: The Study of Two Independent Clinical Cohorts. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27010015"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"125734","DOI":"10.1016\/j.jns.2026.125734","article-title":"Digital biomarkers in early Alzheimer\u2019s disease from wearable or portable technology: A scoping review","volume":"481","author":"Gramkow","year":"2026","journal-title":"J. Neurol. Sci."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/18\/1671\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:21:40Z","timestamp":1789546900000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/18\/1671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":108,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cells15181671"],"URL":"https:\/\/doi.org\/10.3390\/cells15181671","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}