Border-associated macrophages promote cerebral amyloid angiopathy and cognitive impairment through vascular oxidative stress
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Abstract
Background: Cerebral amyloid angiopathy (CAA) is a devastating condition common in patients with Alzheimer’s disease but also observed in the general population. Vascular oxidative stress and neurovascular dysfunction have been implicated in CAA but the cellular source of reactive oxygen species (ROS) and related signaling mechanisms remain unclear. We tested the hypothesis that brain border-associated macrophages (BAM), yolk sac-derived myeloid cells closely apposed to parenchymal and leptomeningeal blood vessels, are the source of radicals through the Aβ-binding innate immunity receptor CD36, leading to neurovascular dysfunction, CAA, and cognitive impairment. Methods: Tg2576 mice and WT littermates were transplanted with CD36 −/− or CD36 +/+ bone marrow at 12-month of age and tested at 15 months. This approach enables the repopulation of perivascular and leptomeningeal compartments with CD36 −/− BAM. Neurovascular function was tested in anesthetized mice equipped with a cranial window in which cerebral blood flow was monitored by laser-Doppler flowmetry. Amyloid pathology and cognitive function were also examined. Results: The increase in blood flow evoked by whisker stimulation (functional hyperemia) or by endothelial and smooth muscle vasoactivity was markedly attenuated in WT → Tg2576 chimeras but was fully restored in CD36 −/− → Tg2576 chimeras, in which BAM ROS production was suppressed. CAA-associated Aβ 1-40 , but not Aβ 1-42 , was reduced in CD36 −/− → Tg2576 chimeras. Similarly, CAA, but not parenchymal plaques, was reduced in CD36 −/− → Tg2576 chimeras. These beneficial vascular effects were associated with cognitive improvement. Finally, CD36 −/− mice were able to more efficiently clear exogenous Aβ 1-40 injected into the neocortex or the striatum. Conclusions: CD36 deletion in BAM suppresses ROS production and rescues the neurovascular dysfunction and damage induced by Aβ. CD36 deletion in BAM also reduced brain Aβ 1-40 and ameliorated CAA without affecting parenchyma plaques. Lack of CD36 enhanced the vascular clearance of exogenous Aβ. Restoration of neurovascular function and attenuation of CAA resulted in a near complete rescue of cognitive function. Collectively, these data implicate brain BAM in the pathogenesis of CAA and raise the possibility that targeting BAM CD36 is beneficial in CAA and other conditions associated with vascular Aβ deposition and damage. Graphical Abstract:
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Lipid droplet-mediated impairment of BAM phagocytosis may lead to insufficient waste clearance, causing excessive deposition of debris such as Aβ.
“Moreover, the LD-mediated impairment of BAM phagocytosis may also lead to insufficient waste clearance at the brain interface and in the perivascular space, causing the excessive deposition of debris, such as Aβ (68, 69).”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [69]
The Discussion (page unavailable) links BAM-generated oxidative stress and neurovascular dysfunction to impaired perivascular Aβ clearance and accumulation. The Methods describe BAM phagocytosis of dextran, but the paper does not link lipid droplets or impaired BAM phagocytosis to Aβ deposition; it proposes a vascular mechanism instead. (LLM, conf=0.87)
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Koemans, E. A., Chhatwal, J. P., van Veluw, S. J., van Etten, E. S., van Osch, M. J. P., van Walderveen, M. A. A., Sohrabi, H. R., Kozberg, M. G., Shirzadi, Z., Terwindt, G. M., et al. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(23)00114-x · Cited by 193 · cited 1× · see citing works
“The leading hypothesis is that CAA results from failure of clearance of neurally-derived Aβ from the perivascular space [2, 6, 11, 102], although uptake from blood or production by mural vascular cells have also been suggested as potential mechanisms [2].”
BackgroundEndothelium-Macrophage Crosstalk Mediates Blood-Brain Barrier Dysfunction in Hypertension
Santisteban, M. M., Ahn, S. J., Lane, D., Faraco, G., García‐Bonilla, L., Racchumi, G., Poon, C., Schaeffer, S. M., Segarra, S. G., Körbelin, J., et al. (2020) · Hypertension · doi:10.1161/hypertensionaha.120.15581 · Cited by 188 · cited 3× · see citing works
“[24–26]).”
BackgroundMethodSelf-citationMechanisms of Bradykinin-Induced Cerebral Vasodilatation in Rats
Sobey, C. G., Heistad, D. D., & Faraci, F. M. (1997) · Stroke · doi:10.1161/01.str.28.11.2290 · Cited by 183 · cited 1× · see citing works
“…cortex with mechanistically distinct vasoactive agents: the endothelial nitric oxide-dependent vasodilator acetylcholine [61], the vasodilator acting through endothelial prostanoids bradykinin [62], or the receptor independent endothelium-dependent vasodilator, the Ca 2 + ionophore A23187 [63–65].”
BackgroundDumas, A. P., Dierksen, G. A., Gurol, M. E., Halpin, A., Martínez‐Ramírez, S., Schwab, K. M., Rosand, J. M., Viswanathan, A., Salat, D. H., Polimeni, J. R., et al. (2012) · Annals of Neurology · doi:10.1002/ana.23566 · Cited by 180 · cited 2× · see citing works
“…flow (CBF) (functional hyperemia), a fundamental homeostatic response of the cerebral microcirculation [15], occurs early in patients with CAA [16–18], whereas Aβ-induced suppression of functional hyperemia and dysfunction of the endothelial regulation of CBF have been linked to CAA in mouse…”
Apoε4 disrupts neurovascular regulation and undermines white matter integrity and cognitive function
Koizumi, K., Hattori, Y., Ahn, S. J., Buendia, I., Ciacciarelli, A., Uekawa, K., Wang, G., Hiller, A., Zhao, L., Voss, H. U., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06301-2 · Cited by 179 · see citing works
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“Aβ does not induce vascular ROS production and neurovascular dysfunction in CD36−/− mice [30, 31], and CD36 in BAM is the specific target of Aβ-induced neurovascular dysfunction and vascular ROS production [25].”
InfluentialSelf-citationTong, X., Nicolakakis, N., Kocharyan, A., & Hamel, É. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4031-05.2005 · Cited by 153 · see citing works
Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy
Peca, S., McCreary, C. R., Donaldson, E., Kumarpillai, G., Shobha, N., Sanchez, K., Charlton, A., Steinback, C. D., Beaudin, A. E., Flück, D., et al. (2013) · Neurology · doi:10.1212/01.wnl.0000435291.49598.54 · Cited by 140 · see citing works
Wilhelmus, M. M. M., Otte-Höller, I., van Triel, J. J. J., Veerhuis, R., Maat-Schieman, M. L. C., Bu, G., de Waal, R. M. W., & Verbeek, M. M. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.070050 · Cited by 138 · cited 3× · see citing works
“Cerebrovascular CD36 expression in AD brains is increased and is linked to CAA [29].”
Park, L., Wang, G., Moore, J. M. R., Girouard, H., Zhou, P., Anrather, J., & Iadecola, C. (2014) · Nature Communications · doi:10.1038/ncomms6318 · Cited by 135 · cited 1× · see citing works
“To test smooth muscle function, the CBF responses to adenosine (400 μM, Sigma) or to the NO donor S-Nitroso-N-acetyl-DL-penicillamine (SNAP; 50 μM, Sigma) were examined [25, 31, 37].”
Self-citationHan, B. H., Zhou, M.-L., Johnson, A. W., Singh, I., Liao, F., Vellimana, A. K., Nelson, J. W., Milner, E., Cirrito, J. R., Basak, J., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1414930112 · Cited by 131 · see citing works
Innate immunity receptor CD36 promotes cerebral amyloid angiopathy
Park, L., Zhou, J., Zhou, P., Pistick, R., Jamal, S. E., Younkin, L. H., Pierce, J. P., Arreguin, A. J., Anrather, J., Younkin, S. G., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300021110 · Cited by 130 · cited 10× · see citing works
“Aβ does not induce vascular ROS production and neurovascular dysfunction in CD36 − / − mice [30, 31], and CD36 in BAM is the specific target of Aβ-induced neurovascular dysfunction and vascular ROS production [25].”
InfluentialSelf-citationKakuda, N., Miyasaka, T., Iwasaki, N., Nirasawa, T., Wada‐Kakuda, S., Takahashi‐Fujigasaki, J., Murayama, S., Ihara, Y., & Ikegawa, M. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0477-x · Cited by 130 · see citing works
Age-Dependent Neurovascular Dysfunction and Damage in a Mouse Model of Cerebral Amyloid Angiopathy
Park, L., Koizumi, K., Jamal, S. E., Zhou, P., Previti, M. L., Nostrand, W. E. V., Carlson, G. A., & Iadecola, C. (2014) · Stroke · doi:10.1161/strokeaha.114.005179 · Cited by 129 · cited 7× · see citing works
“arteries To quantify CAA burden and Aβ-associated fragmentation of smooth muscle cells in pial vessels [20, 31], tangential brain sections were incubated with anti-Aβ (4G8, 1:1,000, mouse; Covance) and the smooth muscle marker anti-α-actin (1:300, rabbit, Abcam) for 48 h.”
BackgroundMethodInfluentialSelf-citationPark, L., Anrather, J., Forster, C. L., Kazama, K., Carlson, G. A., & Iadecola, C. (2004) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000105800.49957.1e · Cited by 128 · cited 1× · see citing works
“The neurovascular dysfunction induced by Aβ is mediated by vascular oxidative stress [42, 69–71].”
BackgroundSelf-citationPolfliet, M. M. J., Goede, P. H., van Kesteren-Hendrikx, E. M. L., van Rooijen, N., Dijkstra, C. D., & van den Berg, T. K. (2001) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(01)00282-x · Cited by 127 · see citing works
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“Optical access to the brain was achieved through a pol-ished and reinforced thinned skull preparation sealed with cyanoacrylate glue and a cover glass [26, 33].”
InfluentialSelf-citationRosenblum, W. I. (1987) · Circulation Research · doi:10.1161/01.res.61.4.601 · Cited by 113 · cited 1× · see citing works
“…cortex with mechanistically distinct vasoactive agents: the endothelial nitric oxide-dependent vasodilator acetylcholine [61], the vasodilator acting through endothelial prostanoids bradykinin [62], or the receptor independent endothelium-dependent vasodilator, the Ca 2 + ionophore A23187 [63–65].”
BackgroundBlood-brain barrier permeability after gamma whole-body irradiation: an in vivo microdialysis study
Diserbo, M., Agin, A., Lamproglou, I., Mauris, J., Staali, F., Multon, É. T., & Amourette, C. (2002) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y02-070 · Cited by 106 · cited 1× · see citing works
“However, experiments were performed 3 months after transplantation when these changes are resolved [97].”
Impaired visual evoked flow velocity response in cerebral amyloid angiopathy
Smith, E. E., Vijayappa, M. B., Lima, F. O., Delgado, P., Wendell, L., Rosand, J. M., & Greenberg, S. M. (2008) · Neurology · doi:10.1212/01.wnl.0000327887.64299.a4 · Cited by 99 · cited 2× · see citing works
“…flow (CBF) (functional hyperemia), a fundamental homeostatic response of the cerebral microcirculation [15], occurs early in patients with CAA [16–18], whereas Aβ-induced suppression of functional hyperemia and dysfunction of the endothelial regulation of CBF have been linked to CAA in mouse…”
Taylor, X., Clark, I., Fitzgerald, G. J., Oluoch, H., Hole, J. T., Demattos, R. B., Wang, Y., & Pan, F. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00649-w · Cited by 98 · see citing works
Wilkinson, K., Boyd, J. D., Glicksman, M. A., Moore, K. J., & Khoury, J. B. E. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.232116 · Cited by 90 · see citing works
Blood flow, capillary transit times, and tissue oxygenation: the centennial of capillary recruitment
Østergaard, L. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00537.2020 · Cited by 90 · see citing works
The Role of Endothelium and Nitric Oxide in Rat Pial Arteriolar Dilatory Responses to CO 2 in vivo
Wang, Q., Pelligrino, D. A., Koenig, H. M., & Albrecht, R. F. (1994) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1994.126 · Cited by 87 · cited 4× · see citing works
“CBF responses to SNAP was reduced in WT → Tg2676 and was improved in CD36 − / − → Tg2676 chimeras (Fig.”
InfluentialNeuropathology of Anti-Amyloid-β Immunotherapy: A Case Report
Castellani, R. J., Shanes, E. D., McCord, M., Reish, N. J., Flanagan, M. E., Mesulam, M. M., & Jamshidi, P. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-221305 · Cited by 84 · cited 1× · see citing works
“Accumulation of perivascular macrophages (CD163+) was also observed around Aβ-laden vessels in a patient who died after Aβ immunotherapy [90].”
BackgroundCD36 in Alzheimer’s Disease: An Overview of Molecular Mechanisms and Therapeutic Targeting
Dobri, A.-M., Dudău, M., Enciu, A., & Hinescu, M. E. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.11.003 · Cited by 82 · cited 1× · see citing works
“The Aβ-binding scavenger receptor CD36 has been linked to AD [27, 28] and is upregulated in CAA [29].”
Chen, X., Liu, X., Koundal, S., Elkin, R., Zhu, X. A., Monte, B., Xu, F., Dai, F., Pedram, M., Lee, H., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00181-4 · Cited by 78 · cited 2× · see citing works
“The leading hypothesis is that CAA results from failure of clearance of neurally-derived Aβ from the perivascular space [2, 6, 11, 102], although uptake from blood or production by mural vascular cells have also been suggested as potential mechanisms [2].”
Garcia-Bonilla, L., Racchumi, G., Murphy, M., Anrather, J., & Iadecola, C. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2980-15.2015 · Cited by 77 · cited 2× · see citing works
“Bone marrow transplantation Procedures for BM transplantation have been previously described [24, 25, 35] and are only summarized.”
BackgroundSelf-citationYang, G., Zhang, Y., Ross, M. E., & Iadecola, C. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00043.2003 · Cited by 74 · see citing works
Self-citationAnfray, A., Schaeffer, S. M., Hattori, Y., Santisteban, M. M., Casey, N., Wang, G., Strickland, M. R., Zhou, P., Holtzman, D. M., Anrather, J., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01757-6 · Cited by 64 · see citing works
Self-citationNitric oxide participates in the cerebrovasodilation elicited from cerebellar fastigial nucleus
Iadecola, C. (1992) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1992.263.5.r1156 · Cited by 62 · cited 3× · see citing works
“All pharmacological agents were dissolved in a modified Ringer’s solu-tion [36].”
MethodSelf-citationLarochelle, A., Bellavance, M., Michaud, J.-P., & Rivest, S. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.09.017 · Cited by 59 · cited 1× · see citing works
“BM transplantation induces severe stress, acute morbidity, and leads to vascular inflammation and BBB opening [96].”
tPA Deficiency Underlies Neurovascular Coupling Dysfunction by Amyloid-β
Park, L., Zhou, J., Koizumi, K., Wang, G., Anfray, A., Ahn, S. J., Seo, J., Zhou, P., Zhao, L., Paul, S. M., et al. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.1140-20.2020 · Cited by 54 · cited 3× · see citing works
“Surgical procedures As described in detail elsewhere [30, 31, 33, 34], mice were anesthetized with isoflurane (induction, 5%; surgery, 1.”
BackgroundMethodSelf-citationMechanisms of myeloid cell entry to the healthy and diseased central nervous system
Amann, L., Masuda, T., & Prinz, M. (2023) · Nature Immunology · doi:10.1038/s41590-022-01415-8 · Cited by 50 · cited 1× · see citing works
“Strong similarities between the transcriptomic profile of BM-derived BAM repopulating the brain and that of native BAM has also been reported [52], supporting the idea that local cues determine myeloid cell identity [98].”
Wang, L., Bao, Y., Yang, Y., Wu, Y., Chen, X., Si, S., & Hong, B. (2010) · SLAS DISCOVERY · doi:10.1177/1087057109359686 · Cited by 49 · see citing works
Cerebral perfusion alterations and cerebral amyloid in autosomal dominant Alzheimer disease
McDade, E., Kim, A. E., James, J. A., Sheu, L. K., Kuan, D. C.-H., Minhas, D. S., Gianaros, P. J., Ikonomović, S., López, O. L., Snitz, B. E., et al. (2014) · Neurology · doi:10.1212/wnl.0000000000000721 · Cited by 48 · see citing works
CD36 gene polymorphism is associated with Alzheimer's disease
Šerý, O., Janoutová, J., Ewerlingová, L., Hálová, A., Lochman, J., Janout, V., Khan, N. A., & Balcar, V. J. (2017) · Biochimie · doi:10.1016/j.biochi.2017.01.009 · Cited by 44 · cited 2× · see citing works
“The Aβ-binding scavenger receptor CD36 has been linked to AD [27, 28] and is upregulated in CAA [29].”
Haematopoietic cells produce BDNF and regulate appetite upon migration to the hypothalamus
Urabe, H., Kojima, H., Chan, L., Terashima, T., Ogawa, N., Katagi, M., Fujino, K., Kumagai, A., Kawai, H., Asakawa, A., et al. (2013) · Nature Communications · doi:10.1038/ncomms2536 · Cited by 41 · cited 1× · see citing works
“Some studies showed replacement of parenchymal cells few weeks after transplant in areas lacking the BBB [54].”
Calcium ionophore and acetylcholine dilate arterioles on the mouse brain by different mechanisms.
Rosenblum, W. I., McDonald, M., & Wormley, B. (1989) · Stroke · doi:10.1161/01.str.20.10.1391 · Cited by 34 · see citing works
Janik, R., Thomason, L. A. M., Chaudhary, S., Dorr, A. E., Scouten, A., Schwindt, G., Masellis, M., Stanisz, G. J., Black, S. E., & Stefanovic, B. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.10.023 · Cited by 28 · cited 1× · see citing works
“In humans with sporadic CAA or with APP mutations resulting in increased brain Aβ, as in corresponding animal models, neurovascular reactivity to neural and/or endothelial stimuli is markedly suppressed [16–18, 59, 60, 75–77].”
Ojo, J. O., Reed, J. M., Crynen, G. C., Vallabhaneni, P., Evans, J., Shackleton, B., Eisenbaum, M., Ringland, C., Edsell, A., MULLAN, M. J., et al. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.658605 · Cited by 21 · cited 1× · see citing works
“Aβ-induced vascular oxidative stress and the attendant neurovascular dysregulation and damage have emerged as key factors in CAA both in mouse models [19, 20] and in humans [22].”
Vargas-Soria, M., Ramos‐Rodríguez, J. J., del Marco, À., Hierro‐Bujalance, C., Carranza-Naval, M. J., Calvo-Rodríguez, M., van Veluw, S. J., Stitt, A. W., Simó, R., Bacskai, B. J., et al. (2022) · Fluids and Barriers of the CNS · doi:10.1186/s12987-022-00380-6 · Cited by 19 · cited 1× · see citing works
“…hyperemia), a fundamental homeostatic response of the cerebral microcirculation [15], occurs early in patients with CAA [16–18], whereas Aβ-induced suppression of functional hyperemia and dysfunction of the endothelial regulation of CBF have been linked to CAA in mouse models [13, 19–21].”
Šerý, O., Zeman, T., Sheardová, K., Vyhnálek, M., Marková, H., Laczó, J., Lochman, J., Králík, P., Vrzalová, K., Dziedzinská, R., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-15299-z · Cited by 17 · cited 2× · see citing works
“In silico studies suggest that the protective SNP may suppress CD36-induced inflammation upon Aβ binding [95].”
Huang, W., Li, R., Zhang, J., Chen, Y., Ramakrishnan, D. P., & Silverstein, R. L. (2022) · Translational research · doi:10.1016/j.trsl.2022.10.005 · Cited by 14 · cited 1× · see citing works
“Approaches to inhibit CD36 have been developed [91–93] and may provide the opportunity to examine their ability to enhance vascular Aβ clearance and reduce vascular damage in a model of ARIA.”
Correlation of gene polymorphisms of CD36 and ApoE with susceptibility of Alzheimer disease
Zhou, L. P., Li, H., Wang, J., Deng, Z., Shan, Y., Tan, S., Shi, Y., Zhang, M.-X., Liu, S.-X., Zhang, B.-J., et al. (2018) · Medicine · doi:10.1097/md.0000000000012470 · Cited by 11 · cited 1× · see citing works
“CD36 single nucleotide polymorphisms (SNP) have been linked to AD, some increasing the risk of AD [28, 94] and others delaying disease onset [94, 95].”
BackgroundRuiz‐Uribe, N. E., Bracko, O., Swallow, M. A., Omurzakov, A., Dash, S., Uchida, H., Xiang, D., Haft‐Javaherian, M., Falkenhain, K., Lamont, M. R. E., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.15.528710 · Cited by 10 · see citing works
Self-citationEvidence for human transmission of amyloid-beta pathology and cerebral amyloid angiopathy
Jaunmuktane, Z., Mead, S., Ellis, M. J., WADSWORTH, J., Nicoll, A., Kenny, J., Launchbury, F., Linehan, J. M., Richard-Loendt, A., Walker, A. S., et al. (2015) · UCL Discovery (University College London) · Cited by 6 · see citing works
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Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets
Guan, F., Wang, R., Yi, Z., Luo, P., Liu, W., Xie, Y., Liu, Z., Xia, Z., Zhang, H., & Cheng, Q. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02124-y · Cited by 371 · see citing works
Beyond the gut: decoding the gut–immune–brain axis in health and disease
Park, J. C., Chang, L., Kwon, H.-K., & Im, S.-H. (2025) · Cellular & Molecular Immunology · doi:10.1038/s41423-025-01333-3 · Cited by 149 · see citing works
“BAMs also regulate BBB permeability through the modulation of vascular oxidative stress, speci fi cally by NADPH oxidase 2 (NOX2), highlighting their critical in fl uence on vascular integrity and neuroimmune communication [180].”
Inflammatory aspects of Alzheimer’s disease
Lucena, P. B., & Heneka, M. T. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02790-2 · Cited by 143 · see citing works
“Deletion of CD36 in BAMs suppressed ROS production and improved neuro-vascular function, with complete rescue of cognitive function [233].”
Neuroinflammation in Alzheimer’s disease: insights from peripheral immune cells
Zhang, Q., Yang, G., Luo, Y., Jiang, L., Chi, H., & Tian, G. (2024) · Immunity & Ageing · doi:10.1186/s12979-024-00445-0 · Cited by 127 · see citing works
Border-associated macrophages in the central nervous system
Sun, R., & Jiang, H. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03059-x · Cited by 107 · see citing works
“In Tg2576 transgenic mice, a model of AD, the deletion of CD36 through PVM repopulation reduced ROS induction and ameliorated neurovascular damage induced by Aβ deposition [117].”
BackgroundTaylor, X., Clark, I., Fitzgerald, G. J., Oluoch, H., Hole, J. T., Demattos, R. B., Wang, Y., & Pan, F. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00649-w · Cited by 98 · see citing works
“Additionally, perivascular macrophages have been shown to protect against bacterial meningitis [12] and to aid in the clearance of vascular Aβ deposition in mouse models of AD [13–16].”
BackgroundThe pathobiology of neurovascular aging
Santisteban, M. M., & Iadecola, C. (2025) · Neuron · doi:10.1016/j.neuron.2024.12.014 · Cited by 94 · see citing works
Self-citationWu, Y., Bogale, T. A., Koıstınaho, J., Pizzi, M., Rõlova, T., & Bellucci, A. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02696-z · Cited by 81 · see citing works
“Brain macrophages are essential sentinels in the immune response as they become activated under brain injury or immunological stimuli [47] and the resulting neuroinflammation can contribute to neurodegeneration both directly as well as by impairing the BBB [56, 102, 118, 135].”
BackgroundBorder-associated macrophages as gatekeepers of brain homeostasis and immunity
Vara‐Pérez, M., & Movahedi, K. (2025) · Immunity · doi:10.1016/j.immuni.2025.04.005 · Cited by 81 · see citing works
Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model
Wu, X., Miller, J. A., Lee, B. T. K., Wang, Y., & Ruedl, C. (2025) · Science Advances · doi:10.1126/sciadv.adq6038 · Cited by 67 · see citing works
“Moreover, the LD-mediated impairment of BAM phagocytosis may also lead to insufficient waste clearance at the brain interface and in the perivascular space, causing the excessive deposition of debris, such as A β ( 68 , 69 ).”
Anfray, A., Schaeffer, S. M., Hattori, Y., Santisteban, M. M., Casey, N., Wang, G., Strickland, M. R., Zhou, P., Holtzman, D. M., Anrather, J., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01757-6 · Cited by 64 · see citing works
“ROS production was assessed with two-photon microscopy in vivo, flow cytometry or brain slices using DHE as a marker 39,41,43 .”
InfluentialSelf-citationSystemic determinants of brain health in ageing
Smith, E. E., Biessels, G. J., Gao, V., Gottesman, R. F., Liesz, A., Parikh, N. S., & Iadecola, C. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-01016-z · Cited by 54 · see citing works
“Border-associated macrophages (BAMs) in the meninges and perivascular space contribute substantially to the cerebral immunological milieu and the pathophysiology of cognitive decline in vascular and amyloid-related dementia 166,167 .”
Self-citationShi, M., Chu, F., Zhu, F., & Zhu, J. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-023-03003-5 · Cited by 50 · see citing works
“The absence of CD36 in BAM also declines brain Aβ40 without affecting plaques in the brain, and enhanced the vascular clearance of exogenous Aβ [107].”
BackgroundEndothelial cells and macrophages as allies in the healthy and diseased brain
Dénes, Á., Hansen, C. E., Oezorhan, U., Figuerola, S., de Vries, H. E., Sorokin, L. M., Planas, A. M., Engelhardt, B., & Schwaninger, M. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02695-0 · Cited by 49 · see citing works
Zhan, X., Wang, S., Bèchet, N. B., Gouras, G. K., & Wen, G. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07592-2 · Cited by 45 · see citing works
“Deletion of CD36 from PVMs improved neurovascular function, reduced ROS production, and decreased A β 40 in blood vessels [100].”
Albertini, G., Zielonka, M., Cuypers, M., Snellinx, A., Xu, C., Poovathingal, S. K., Wojno, M., Davie, K., van Lieshout, V., Craessaerts, K., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-02125-8 · Cited by 47 · see citing works
“Alternatively, activation of Fc or complement receptors on border-associated macrophages by the Fc moiety of Lecanemab could also trigger harmful vascular responses 34 .”
The role of neuroinflammation in cerebral amyloid angiopathy
van den Brink, H., Voigt, S., Kozberg, M., & van Etten, E. S. (2024) · eBioMedicine · doi:10.1016/j.ebiom.2024.105466 · Cited by 39 · see citing works
The vascular contribution to cognitive decline in ageing and dementia
Anderle, S., Dixon, M., Quintela‐López, T., Sideris-Lampretsas, G., & Attwell, D. (2025) · Nature reviews. Neuroscience · doi:10.1038/s41583-025-00950-1 · Cited by 38 · see citing works
The immunology of stroke and dementia
Iadecola, C., & Anrather, J. (2025) · Immunity · doi:10.1016/j.immuni.2024.12.008 · Cited by 32 · see citing works
Self-citationGreenberg, S. M., & van Veluw, S. J. (2024) · Stroke · doi:10.1161/strokeaha.124.044293 · Cited by 29 · see citing works
Bonnar, O., Eyre, B., & van Veluw, S. J. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00535 · Cited by 33 · see citing works
“Transplantation of CD36 depleted bone marrow, from which BAMs were then derived, resulted in fewer reactive oxygen species in BAMs, a striking reduction in CAA and improved clearance of A β [107].”
Mouse and human macrophages and their roles in cardiovascular health and disease
Gallerand, A., Han, J., Ivanov, S., & Randolph, G. J. (2024) · Nature Cardiovascular Research · doi:10.1038/s44161-024-00580-3 · Cited by 25 · see citing works
“While the function of these macrophages is under intense investigation, it is nonetheless clear that these macrophages, especially those expressing LYVE1, participate critically in vascular homeostasis and extracellular matrix (ECM) remodeling 44,86,90,92–94 (Figs.”
Immune dysfunction in Alzheimer disease
Butovsky, O., Rosenzweig, N., Kleemann, K. L., Jorfi, M., Kuchroo, V. K., Tanzi, R. E., & Weiner, H. L. (2025) · Nature reviews. Neuroscience · doi:10.1038/s41583-025-00997-0 · Cited by 34 · see citing works
“CD36-mediated recognition of Aβ was associated with detrimental reactive oxygen species (ROS) production and cerebrovascular damage, whereas the transplantation of bone marrow from CD36 –/– mice into AD mice improved Aβ clearance and cognition 107 .”
The role of macrophage plasticity in neurodegenerative diseases
Ma, H., Zhu, M., Chen, M., Li, X., & Feng, X. (2024) · Biomarker Research · doi:10.1186/s40364-024-00624-7 · Cited by 24 · see citing works
“When PVMs are depleted in TgCRND8 mice using chloroform, Aβ deposition around cerebral blood vessels is increased [121, 122].”
BackgroundChanges in border-associated macrophages after stroke: Single-cell sequencing analysis
Yu, N., Zhao, Y., Wang, P., Zhang, F., Wen, C., & Wang, S.-L. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-01092 · Cited by 24 · see citing works
“The datasets we analyzed at 1 and 2 days post-ischemic stroke correspond to the acute phase of stroke.”
Brain macrophages in vascular health and dysfunction
Bijnen, M., Sridhar, S., Keller, A., & Greter, M. (2024) · Trends in Immunology · doi:10.1016/j.it.2024.11.012 · Cited by 19 · see citing works
Niche-specific therapeutic targeting of myeloid cells in the central nervous system
Frosch, M., & Prinz, M. (2025) · Immunity · doi:10.1016/j.immuni.2025.03.016 · Cited by 17 · see citing works
Novel Perivascular Macrophage Mechanism to Promote Glymphatic Aβ Clearance After Stroke
Li, C., Li, T., Hu, M., Kang, X., Su, X., Wang, S., Lu, D., Shen, S., Huang, H., Deng, X., et al. (2025) · Stroke · doi:10.1161/strokeaha.124.050266 · Cited by 17 · see citing works
García, F., & Heiman, M. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00799-z · Cited by 14 · see citing works
“Recent work has highlighted the role of APOE ε4 genotype and BAMs in the pathogenesis of CAA, noting these cells as a cellular source of reactive oxygen species and consequently, inducing neuro-vascular dysfunction [184, 185].”
Perivascular macrophages in cerebrovascular diseases
Uchikawa, H., Uekawa, K., & Hasegawa, Y. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.114680 · Cited by 14 · see citing works
Self-citationCerebrovascular Endothelial Dysfunction: Role of BACE1
Katušić, Z. S., d’Uscio, L. V., & He, T. (2024) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.124.320798 · Cited by 14 · see citing works
Zou, J., Lin, R., Miao, Y., Xie, M., Wang, X., Gao, L., Huang, X., & Guo, Y. (2024) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2024.07.005 · Cited by 14 · see citing works
Therapeutic targeting of neuroimmune mechanisms in neurodegeneration
Monroe, K. M., Hong, S. Y., Lewcock, J. W., & Yang, A. C. (2026) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01370-7 · Cited by 14 · see citing works
Neuroimmunology of Cardiovascular Disease
Zarate, S. M., Kirabo, A., Hinton, A. O., Jr., & Santisteban, M. M. (2024) · Current Hypertension Reports · doi:10.1007/s11906-024-01301-8 · Cited by 13 · see citing works
Luo, L., Que, M., Zeng, L., Wang, X., Sun, T., Zhou, Z., Zhao, Y., Li, S., & Luo, A. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107947 · Cited by 11 · see citing works
Immune system activation and cognitive impairment in arterial hypertension
Schreiber, S., Arndt, P., Morton, L., Garza, A. P., Müller, P., Neumann, K., Mattern, H., Dörner, M., Bernal, J., Vielhaber, S., et al. (2024) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00219.2024 · Cited by 12 · see citing works
Li, T., Zhang, J., Song, H., Zhang, R., Fan, F., Huang, Z., Zeng, M., Peng, B., & Zhang, J. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03631-z · Cited by 10 · see citing works
“In the CNS, CD36 acts as an important receptor for Aβ-induced oxidative stress and neurovascular damage, inducing Aβ accumulation and ROS generation in BAMs [16], which is closely related to the progression of diseases like CAA and AD.”
Anwer, M., Poliakova, T., Albanus, R. D., Bhuiyan, M. I. H., Brickman, A. M., Chaudhuri, S., Cuddy, L. K., Eisenbaum, M., Foley, K. E., Gould, D. B., et al. (2026) · Mammalian Genome · doi:10.1007/s00335-026-10210-x · Cited by 9 · see citing works
“Even when aged to 15 months, CD36 depletion in BAM rescues neuro - vascular and cognitive dysfunction in these mice which was accompanied in CAA but not parenchymal plaque reduction (Uekawa et al. 2023).”
Self-citationFliegauf, M., Levard, D., Cardamone, F., Frosch, M., Kuhn, S., Sankowski, R., Provinciali, M., Dumas, A. A., Gasull, A. D., Aktories, P., et al. (2026) · Nature Immunology · doi:10.1038/s41590-026-02457-y · Cited by 11 · see citing works
“…the systemic route of LPS delivery, effects mediated by peripheral immune reactions cannot be fully ruled out as a confounding variable. sdCAMs have been implicated in many CNS diseases, such as cerebral aneurysm formation 55 , ischemic stroke 45,47,51 or neurodegenerative disorders 26,27,56,57 .”
Martin, M., Boulaire, M., Lucas, C., Peltier, A., Pourtau, L., Gaudout, D., Layé, S., Pallet, V., Joffre, C., & Dinel, A. (2024) · Journal of Nutrition · doi:10.1016/j.tjnut.2024.09.015 · Cited by 9 · see citing works
Hu, M., Yi, H., Wang, S., Kang, X., Liu, Y., Liu, Z., Huang, H., Qin, Q., Yuan, L., Cai, W., et al. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-01273 · Cited by 10 · see citing works
Border-associated macrophages: From physiology to therapeutic targets in Alzheimer's disease
Zheng, F., Dong, T., Chen, Y., Wang, L., & Peng, G. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.115021 · Cited by 8 · see citing works
“Interestingly, Uekawa et al. find that the absence of CD36 in pvM Φ can also enhance the clearance rate of soluble A β and improve vascular A β deposition but not affect parenchymal plaques (Uekawa et al., 2023).”
BackgroundMethodBorder‐Associated Macrophages: From Embryogenesis to Immune Regulation
Zhan, T., Tian, S., & Chen, S. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70105 · Cited by 7 · see citing works
Xiong, X.-Y., Yuan, H., Mu, Y., He, Y., Xie, F., Feng, X., Xie, J., Pan, X., Wang, Y.-F., Gong, J., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1625673 · Cited by 8 · see citing works
CNS border macrophages in health and disease
Fliegauf, M., Amann, L., & Prinz, M. (2026) · The Journal of Immunology · doi:10.1093/jimmun/vkaf308 · Cited by 5 · see citing works
Hoyer-Kimura, C. H., & Hay, M. (2026) · Experimental Neurology · doi:10.1016/j.expneurol.2026.115815 · Cited by 5 · see citing works
Shen, X., Zheng, C., Lin, R., Wang, J., & Chen, Z. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1795042 · Cited by 5 · see citing works
“Border-associated macrophages (BAMs), acting as perivascular innate immune sentinels, are vital in regulating blood-brain barrier permeability, clearing A b (in AD models), and initiating T cell responses as antigen-presenting cells (e.g., in Parkinson ’ s disease a -synuclein models) (113, 126).”
Frontiers of Neurodegenerative Disease Treatment: Targeting Immune Cells in Brain Border Regions
Satyanarayanan, S. K., Han, Z., Xiao, J., Yuan, Q., Yung, W., Ke, Y., Chang, R. C., Zhu, M. H., Su, H., Su, K. P., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.10.007 · Cited by 5 · see citing works
Functional border-associated macrophages limit Alzheimer’s Disease progressionPreprint
Adler, D. I., Pinheiro-Rosa, N., Millet, A., Gajic, Z. Z., Cheng, E., Gamallo‐Lana, B., Morizawa, Y. M., Klann, E., Gan, W., Mar, A. C., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.31.703045 · Cited by 8 · see citing works
Zhao, P., Li, S., Liu, Q., Peng, X.-C., Liu, L., Yang, F.-Y., Wang, C., Qian, F., & Tang, F.-R. (2026) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2026.1726194 · Cited by 5 · see citing works
tPA supplementation preserves neurovascular and cognitive function in Tg2576 mice
Uekawa, K., Anfray, A., Ahn, S. J., Casey, N., Seo, J., Zhou, P., Iadecola, C., & Park, L. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13878 · Cited by 4 · see citing works
“Considering the link between CAA burden and cognitive function, 14,42,43,50 we further investigated whether the improvement in the nest building behavior is associated with a reduction in CAA.”
BackgroundMethodInfluentialSelf-citationWITHDRAWN: Border-associated macrophages in the central nervous system
Sun, R., & Jiang, H. (2024) · Clinical Immunology · doi:10.1016/j.clim.2024.109921 · Cited by 4 · see citing works
RetractedRoles of central nervous system resident and recruited macrophages in the brain barrier system
Liu, Z., Cheng, T., Dong, H., Sun, D., Wang, Y., Li, J., Yu, Z., & Cao, L. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00986 · Cited by 3 · see citing works
Lao, K., Li, Y., Xiao, Y., Sun, Y., Dai, Y., Li, H., Yang, Y., Zhang, Y., Wang, J., Li, W., et al. (2026) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2026.2645483 · Cited by 3 · see citing works
“…stress reciprocally enhances aβ deposition and tau hyperphosphorylation, creating a pathogenic feed-back loop that exacerbates neurodegeneration 12 . the Keap1-Nrf2-aRe signalling axis serves as a main regulator of cellular redox homeostasis, orchestrating the expression of cytoprotective…”
Spatial atlas of the human brain vasculature reveals specialized cell ensembles
Wang, J. C., Sanchez, D., Arul, S., Gülsuyu, B., Gopinadhan, A., Mukhtar, T., Kim, J., Andrews, J. P., Williams, M. A. C., Jung, Y., et al. (2026) · Cell · doi:10.1016/j.cell.2026.07.007 · Cited by 4 · see citing works
Otero, A. M., & Antonson, A. M. (2025) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2025.1677414 · Cited by 2 · see citing works
Ricaurte‐Fajardo, A., Ivanidze, J., Zhang, D., Mahmud, M., Yasen, W., Ravdin, L., Pahlajani, S. S., de Leon, M., Nordvig, A. S., & Chiang, G. C.-Y. (2025) · American Journal of Neuroradiology · doi:10.3174/ajnr.a8654 · Cited by 1 · see citing works
Hou, C., Liu, Q. T., Dai, Y., Xu, J., Ren, W., Wang, B., Tang, T., Fu, B., Luo, Y., Shan, Y., et al. (2026) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x261415782 · Cited by 1 · see citing works
Liu, X., Li, M., Wei, Z., Shang, T., & Zou, W. (2026) · ASN NEURO · doi:10.1080/17590914.2026.2687503 · Cited by 1 · see citing works
“…b to CD36 on BAM surfaces induces reactive oxygen species (ROS) production, thereby promoting neurovascular dysfunction and cognitive impairment; genetic or functional loss of CD36 suppresses ROS generation and mitigates A b -induced neurovascular deficits (Park et al., 2017; Uekawa et al., 2023).”
Fawzy, M. N. (2026) · Inflammopharmacology · doi:10.1007/s10787-026-02363-7 · Cited by 1 · see citing works
“In AD mouse models, BAMs have been shown to internalize Aβ from the perivascular space, and their dysfunction correlates with cerebral amyloid angiopathy (Zhan et al. 2025a; Uekawa et al. 2023).”
The Alzheimer’s therapeutic Lecanemab induces an amyloid-clearing program in microgliaPreprint
Albertini, G., Zielonka, M., Marie-Lynn, C., Snellinx, A., Xu, C., Suresh, P., Marta, W., Davie, K., Veerle, V. L., Craessaerts, K., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.24.666347 · Cited by 1 · see citing works
“Alternatively, the Fc moiety of Lecanemab may activate Fc receptors or complement receptors in border associated macrophages potentially triggering damaging responses in the vasculature 34 .”
Plowey, E. D., Abettan, J., Chou, P. C., Lye‐Barthel, M., Amaral, A. C. S., Sebalusky, J., Hamann, S., Srinivasan, J., Brown, R. Z., Fang, Q., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.30.702402 · Cited by 1 · see citing works
In conversation with Costantino Iadecola
Floriddia, E. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01505-2
Qiang, W., Deng, W.-J., Song, S.-L., & Pan, L.-H. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e37101
“Limited researches have been conducted on immune cell subpopulations in cognitive impairment mice which has led to inconsistent findings [28,29].”
BackgroundAssociation between CD36 and ischemic stroke: consequential or coincidental?
Dobri, A.-M., Popescu, I. D., Codrici, E., Dudău, M., Enciu, A., & Tănase, C. (2025) · Exploration of neuroscience · doi:10.37349/en.2025.100688
The Neuroimmune Landscape of the Lysosomal Storage Disorder Sanfilippo Syndrome
Badell‐Grau, R. A., & Schlachetzki, J. C. M. (2025) · BioEssays · doi:10.1002/bies.70083
Mechanisms of Dural Involvement in Cerebral Amyloid Angiopathy
Zedde, M., Piazza, F., & Pascarella, R. (2025) · Cells · doi:10.3390/cells15010026
“Another limitation is the insufficient examination and description of the dura mater in both animal and human biopsy specimens, where observations tend to focus on leptomeningeal and cortical small vessels rather than pachymeningeal arterioles [21].”
Zhou, L., Xu, Y., Yang, P., Zhou, J., Wang, M., Li, Y., Yang, X., Liu, X., Wang, T., Yao, C., et al. (2026) · ACS Nano · doi:10.1021/acsnano.5c16884
Engulfment by brain macrophages in a short-lived vertebratePreprint
Nagvekar, R., Pogson, A. N., Kalakuntla, P. R., Barr, H. J., Jaimes, A. M. M., Perry, S., Costa, E. K., Chen, J., Boos, F., Negredo, P. N., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.28.721434
Hoyer-Kimura, C. H., Konhilas, J. P., Ryan, L., Sweitzer, N. K., Bull, D. A., & Hay, M. (2026) · Research Square · doi:10.21203/rs.3.rs-9296663/v1
“In patients undergoing cardiac surgery, perioperative increases in plasma NfL have been associated with delirium and longer-term cognitive decline, while higher baseline NfL levels reflect preexisting neuronal vulnerability (9), (10), (11).”
Hardwired and rewired: Tissue macrophages in homeostasis and cancer
Mohei, H., Deren, D. A. V., & Haldar, M. (2026) · Journal of Leukocyte Biology · doi:10.1093/jleuko/qiag046
A perivascular perspective on the immune impacts in cerebral amyloid angiopathy
Eyre, B., & Bonney, S. K. (2026) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x261454165
Zhao, X., Zhang, G., Wang, Z., Zhang, D. J., Xia, Z., & Huo, C. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1893167
“…parallel, border-associated macrophages located at meningeal, perivascular, and choroid plexus interfaces are strategically positioned to sample CSF-or vessel-associated antigens, respond to vascular and in fl am-matory cues, and participate in antigen presentation to adaptive immune cells (35, 36).”
Marshall, C. R., Moser, F. A., Scott, C. F., Ventura‐Antunes, L., Romero‐Fernandez, W., Migas, L. G., Tideman, L. E. M., Colley, M. E., Dufresne, M., Schrag, M., et al. (2026) · Acta Neuropathologica Communications · doi:10.1186/s40478-026-02361-4 · Cited by 1 · see citing works
“[70],[74][75][76][77][78][79][80][81] This proposes a potential role of GM1 in vascular amyloid deposition and supports the idea that some overlapping lipid-mediated mechanisms may contribute to both neuritic and vascular β -amyloid aggregation .”
Brain macrophages in neurodegeneration
Johnston, R. J., Torres, N. A. P., Li, Y., & Han, C. Z. (2026) · Advances in immunology · doi:10.1016/bs.ai.2026.06.005
Engulfment by brain macrophages in a short-lived vertebratePreprint
Nagvekar, R., Pogson, A. N., Kalakuntla, P. R., Barr, H. J., Jaimes, A. M. M., Perry, S., Costa, E. K., Chen, J., Boos, F., Negredo, P. N., et al. (2026) · eLife · doi:10.7554/elife.112503.1
Engulfment by brain macrophages in a short-lived vertebratePreprint
Nagvekar, R., Pogson, A. N., Kalakuntla, P. R., Barr, H. J., Jaimes, A. M. M., Perry, S., Costa, E. K., Chen, J., Boos, F., Negredo, P. N., et al. (2026) · eLife · doi:10.7554/elife.112503
Neurodegeneration as a dysregulation of neuroimmune crosstalk
Bennett, F. C., Hong, S. Y., Jiang, N. J., & Marazzi, I. (2026) · Cell · doi:10.1016/j.cell.2026.07.015 · Cited by 2 · see citing works
“116 Depletion or perturbation of BAMs in AD mouse models can alter pathological features, including aggregate burden and vascular dysfunction, supporting a potential functional role in disease.”
Liao, J., Chen, Y., Lu, Y., Qu, F., Xie, X., Yang, Z., & Wen, W. (2026) · Behavioural Neurology · doi:10.1155/bn/6222269
Chmiel, J., & Kopańska, M. (2026) · Cells · doi:10.3390/cells15181671
“Thus, the relevant disease transition is not a simple switch from a universally beneficial to a universally harmful macrophage population, but a change in subset, anatomical niche, and functional state under sustained amyloid and vascular stress [26–28].”
Influential
- Authors
- Uekawa, K., Hattori, Y., Ahn, S. J., Seo, J., Casey, N., Anfray, A., Zhou, P., Luo, W., Anrather, J., Park, L., & Iadecola, C.
- Affiliations
- Weill Cornell Medicine (US)
- Corresponding author
- Park, Laibaik
- Iadecola, Costantino
- ORCID
- Venue
- Molecular Neurodegeneration
- Published
- 2023-10-03
- Volume
- 18
- Issue
- 1
- Pages
- 73-73
- ISSN
- 1750-1326 (ISSN-L)
- PMC
- PMC10548599
- OpenAlex
- W4387311036
- Cited by
- 80
- References
- 105
- Citations by year
- 2026: 27 · 2025: 26 · 2024: 25 · 2023: 2
- FWCI
- 14.21
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-07-12)
- Open access
- gold
- doi.org
- Locations
- Molecular Neurodegeneration (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (NS37853)
- National Institute of Health (NS097805)
- Japan Heart Foundation/Bayer Research Grant Abroad
- The Uehara Memorial Foundation Research Fellowship
- Japan Society for the Promotion of Science Overseas Research Fellowships
- Leon Levy Foundation
- BrightFocus Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- cerebral amyloid angiopathy, border-associated macrophages, CD36, reactive oxygen species, vascular oxidative stress, neurovascular dysfunction, Aβ40, cognitive impairment, Alzheimer's disease, bone marrow transplantation, functional hyperemia, cerebral blood flow, amyloid-beta clearance, Tg2576 mice, innate immunity, perivascular macrophages
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