APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline
Open accessAbstract
Vascular contributions to dementia and Alzheimer's disease are increasingly recognized 1-6. Recent studies have suggested that breakdown of the blood-brain barrier (BBB) is an early biomarker of human cognitive dysfunction 7, including the early clinical stages of Alzheimer's disease 5,8-10. The E4 variant of apolipoprotein E (APOE4), the main susceptibility gene for Alzheimer's disease 11-14, leads to accelerated breakdown of the BBB and degeneration of brain capillary pericytes 15-19, which maintain BBB integrity 20-22. It is unclear, however, whether the cerebrovascular effects of APOE4 contribute to cognitive impairment. Here we show that individuals bearing APOE4 (with the ε3/ε4 or ε4/ε4 alleles) are distinguished from those without APOE4 (ε3/ε3) by breakdown of the BBB in the hippocampus and medial temporal lobe. This finding is apparent in cognitively unimpaired APOE4 carriers and more severe in those with cognitive impairment, but is not related to amyloid-β or tau pathology measured in cerebrospinal fluid or by positron emission tomography 23. High baseline levels of the BBB pericyte injury biomarker soluble PDGFRβ 7,8 in the cerebrospinal fluid predicted future cognitive decline in APOE4 carriers but not in non-carriers, even after controlling for amyloid-β and tau status, and were correlated with increased activity of the BBB-degrading cyclophilin A-matrix metalloproteinase-9 pathway 19 in cerebrospinal fluid. Our findings suggest that breakdown of the BBB contributes to APOE4-associated cognitive decline independently of Alzheimer's disease pathology, and might be a therapeutic target in APOE4 carriers.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
APOE4 induces cognitive decline independent of Aβ or tau pathology probably through the CypA-MMP9 pathway.
“APOE4 even induces cognitive decline independent of Aβ or tau pathology probably through CypA-MMP9 pathway.185”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [185]
The introductory discussion says BBB breakdown contributes to cognitive decline in APOE4 carriers independently of Alzheimer’s pathology, and that APOE4 activates the CypA-MMP9 pathway. It presents the pathway’s role in subsequent dysfunction as a possibility, however; the claim overstates the human findings by saying APOE4 induces cognitive decline as an established causal result. (LLM, conf=0.83)
Experimental — accuracy not yet measuredCompared with wild-type mice, both Apoe knockout mice and mice expressing APOE4 have a leaky BBB, a phenomenon also reported in cognitively unimpaired and mildly impaired individuals who carry an APOEε4 allele.
“When compared with wild-type mice, both Apoe knockout mice and mice expressing APOE4 have a leaky BBB, a phenomenon also reported in cognitively unimpaired and mildly impaired individuals who carry an APOEε4 allele183–185.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [185]
The Introductory Paragraph reports BBB breakdown in cognitively normal APOE4 carriers, with greater breakdown in carriers with mild cognitive impairment. It mentions APOE knock-in mice and mouse pericytes in connection with a molecular pathway, but does not report the claimed BBB-leak comparison between wild-type, Apoe knockout, and APOE4-expressing mice. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPeripheral APOE seems to influence the brain partly by impacting the BBB.
“peripheral APOE seems to influence the brain partly by impacting the BBB.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [185]
The Introductory Paragraph reports BBB breakdown in APOE4 carriers and suggests that it contributes to cognitive decline. It does not distinguish peripheral APOE from APOE produced within the brain, so it does not establish that peripheral APOE acts through the BBB. (LLM, conf=0.86)
Experimental — accuracy not yet measuredBreakdown of the blood-brain barrier is an early biomarker of human cognitive decline.
“Breakdown of the blood-brain barrier (BBB) is an early biomarker of human cognitive decline”
From ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease (2022) · cites this paper as Montagne et al 2020
The Introductory Paragraph says recent studies have suggested that BBB breakdown is an early biomarker of human cognitive dysfunction. This paper also reports that a BBB pericyte-injury biomarker predicted future cognitive decline, but specifically in APOE4 carriers, not non-carriers. The claim presents the broader biomarker proposition as established rather than suggested. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAPOE4 alters blood-brain barrier integrity, influencing metabolite exchange between the periphery and CNS, including reduced brain glucose and lipid transport.
“APOE4 alters the integrity of the blood brain barrier (BBB) influencing metabolite exchange between the periphery and the central nervous system (CNS) including reduced brain glucose and lipid transport [17][18][19] .”
From APOE4-drives brain bioenergetic shifts independent of Alzheimer’s disease pathology (2026) · cites this paper as [19]
The Introductory Paragraph reports greater blood–brain barrier permeability in APOE4 carriers, supporting the claim that APOE4 alters barrier integrity. It does not establish reduced brain glucose or lipid transport, or measure metabolite exchange between the periphery and CNS; searches for those transport claims found no supporting passage in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
ApoE4 exhibits direct toxic effects on cerebrovasculature independently of amyloid and tau pathologies.
“apoE4 exhibits direct toxic effects on cerebrovasculature independently of amyloid and tau pathologies”
From ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease (2022) · cites this paper as Montagne et al 2020
Existing cerebrovascular-function-modulating therapeutics eventually failed to alleviate cognitive deficits in AD patients and AD model mice.
“However, these efforts eventually failed to alleviate the cognitive deficits in AD patients and AD model mice,[ 7 , 8 ]”
From Multifunctional Nanostructure RAP‐RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit (2021) · cites this paper as [8]
The Introductory Paragraph discusses blood–brain barrier breakdown and proposes CypA inhibitors as a possible future treatment. It also reports that pathway blockade restored blood–brain barrier integrity and neuronal and synaptic functions in APOE4 knock-in mice. Our copy does not report that existing cerebrovascular therapies failed to alleviate cognitive deficits in AD patients or AD model mice; searches for treatment failure and cognitive outcomes found no such passage. (LLM, conf=0.74)
Experimental — accuracy not yet measuredAs individuals age, there is a decline in the efficiency of glymphatic transport mechanisms in eliminating waste products such as Aβ.
“As individuals age, there is a decline in the efficiency of these transport mechanisms in eliminating waste products such as Aβ.156,157”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [156]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Desikan, R. S., Ségonne, F., Fischl, B., Quinn, B. T., Dickerson, B. C., Blacker, D., Buckner, R. L., Dale, A. M., Maguire, R. P., Hyman, B. T., et al. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.01.021 · Cited by 13,324 · see citing works
Jenkinson, M., Bannister, P., Brady, M., & Smith, S. (2002) · NeuroImage · doi:10.1006/nimg.2002.1132 · Cited by 11,888 · see citing works
NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537 · see citing works
The Clinical Dementia Rating (CDR): Current version and scoring rules
Morris, J. C. (1993) · Neurology · doi:10.1212/wnl.43.11.2412-a · Cited by 9,882 · see citing works
Self-citationFischl, B. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.01.021 · Cited by 9,526 · see citing works
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · see citing works
Fischl, B., Salat, D. H., Busa, E., Albert, M., Dieterich, M., Haselgrove, C., van der Kouwe, A., Killiany, R., Kennedy, D., Klaveness, S., et al. (2002) · Neuron · doi:10.1016/s0896-6273(02)00569-x · Cited by 8,610 · see citing works
Measuring the thickness of the human cerebral cortex from magnetic resonance images
Fischl, B. R., & Dale, A. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.200033797 · Cited by 5,789 · see citing works
Wardlaw, J. M., Smith, E. E., Biessels, G. J., Cordonnier, C., Fazekas, F., Frayne, R., Lindley, R. I., O'Brien, J. T., Barkhof, F., Benavente, O. R., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70124-8 · Cited by 5,560 · see citing works
Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.188 · Cited by 3,076 · see citing works
Self-citationPericytes regulate the blood–brain barrier
Armulik, A., Genové, G., Mäe, M., Nisancioglu, M. H., Wallgard, E., Niaudet, C., He, L., Norlin, J., Lindblom, P., Strittmatter, K., et al. (2010) · Nature · doi:10.1038/nature09522 · Cited by 2,843 · see citing works
The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease
Iadecola, C. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.030 · Cited by 2,480 · see citing works
Blood-brain barrier breakdown in the aging human hippocampus
Montagne, A., Barnes, S. R., Sweeney, M. D., Halliday, M. R., Sagare, A. P., Zhao, Z., Toga, A. W., Jacobs, R. E., Liu, C. Y., Amezcua, L., et al. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.032 · Cited by 2,102 · see citing works
Self-citationBlood–brain barrier breakdown is an early biomarker of human cognitive dysfunction
Nation, D. A., Sweeney, M. D., Montagne, A., Sagare, A. P., D’Orazio, L. M., Pachicano, M., Sepehrband, F., Nelson, A. R., Buennagel, D. P., Harrington, M. G., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0297-y · Cited by 1,728 · see citing works
Self-citationGlickman, M. E., Rao, S. R., & Schultz, M. R. (2014) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2014.03.012 · Cited by 1,561 · see citing works
Bell, R. D., Winkler, E. A., Sagare, A. P., Singh, I., LaRue, B., Deane, R., & Zlokovic, B. V. (2010) · Neuron · doi:10.1016/j.neuron.2010.09.043 · Cited by 1,448 · see citing works
Self-citationApolipoprotein E controls cerebrovascular integrity via cyclophilin A
Bell, R. D., Winkler, E. A., Singh, I., Sagare, A. P., Deane, R., Wu, Z., Holtzman, D. M., Betsholtz, C., Armulik, A., Sallstrom, J., et al. (2012) · Nature · doi:10.1038/nature11087 · Cited by 1,293 · see citing works
Self-citationIturria-Medina, Y., Sotero, R. C., Toussaint, P. J., Mateos-Pérez, J. M., Evans, A. C., Initiative, T. A. D. N., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., et al. (2016) · Nature Communications · doi:10.1038/ncomms11934 · Cited by 1,202 · see citing works
Self-citationAggarwal, C. C. (2013) · Springer eBooks · doi:10.1007/978-1-4614-6396-2 · Cited by 1,110 · see citing works
Morris, J. C., Weintraub, S., Chui, H. C., Cummings, J., DeCarli, C., Ferris, S., Foster, N. L., Galasko, D., Graff-Radford, N., Peskind, E. R., et al. (2006) · Alzheimer Disease & Associated Disorders · doi:10.1097/01.wad.0000213865.09806.92 · Cited by 950 · see citing works
Self-citationThe Alzheimer's Disease Centers' Uniform Data Set (UDS)
Weıntraub, S., Salmon, D. P., Mercaldo, N. D., Ferris, S. H., Graff‐Radford, N. R., Chui, H. C., Cummings, J. L., DeCarli, C. S., Foster, N. L., Galasko, D. R., et al. (2009) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e318191c7dd · Cited by 885 · see citing works
Self-citationQuantification of Five Neuropsychological Approaches to Defining Mild Cognitive Impairment
Jak, A. J., Bondi, M. W., Delano-Wood, L., Wierenga, C., Corey-Bloom, J., Salmon, D. P., & Delis, D. C. (2009) · The American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e31819431d5 · Cited by 823 · see citing works
Impact of multiple pathologies on the threshold for clinically overt dementia
Kapasi, A., DeCarli, C., & Schneider, J. A. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1717-7 · Cited by 739 · see citing works
APOE and Alzheimer disease: a major gene with semi-dominant inheritance
Genin, E., Hannequin, D., Wallon, D., Sleegers, K., Hiltunen, M., Combarros, O., Bullido, M. J., Engelborghs, S., De Deyn, P., Berr, C., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.52 · Cited by 714 · see citing works
Vascular dysfunction—The disregarded partner of Alzheimer's disease
Sweeney, M. D., Montagne, A., Sagare, A. P., Nation, D. A., Schneider, L. S., Chui, H. C., Harrington, M. G., Pa, J., Law, M., Wang, D. J. J., et al. (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.07.222 · Cited by 711 · see citing works
Self-citationAPOLIPOPROTEIN E ALLELES AS RISK FACTORS IN ALZHEIMER'S DISEASE
Roses, M. D. (1996) · Annual Review of Medicine · doi:10.1146/annurev.med.47.1.387 · Cited by 707 · see citing works
Alzheimer’s disease: A matter of blood–brain barrier dysfunction?
Montagne, A., Zhao, Z., & Zlokovic, B. V. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20171406 · Cited by 672 · see citing works
Self-citationHalliday, M. R., Rege, S. V., Ma, Q., Zhao, Z., Miller, C. A., Winkler, E. A., & Zlokovic, B. V. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2015.44 · Cited by 649 · see citing works
Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease
van de Haar, H. J., Burgmans, S., Jansen, J. F. A., van Osch, M. J. P., van Buchem, M. A., Muller, M., Hofman, P. A. M., Verhey, F. R. J., & Backes, W. H. (2016) · Radiology · doi:10.1148/radiol.2016152244 · Cited by 601 · see citing works
Version 3 of the National Alzheimer’s Coordinating Center’s Uniform Data Set
Besser, L. M., Kukull, W. A., Knopman, D. S., Chui, H. C., Galasko, D., Weıntraub, S., Jicha, G. A., Carlsson, C. M., Burns, J. M., Quinn, J. F., et al. (2018) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000279 · Cited by 511 · see citing works
Self-citationMicrovascular injury and blood–brain barrier leakage in Alzheimer's disease
Zipser, B. D., Johanson, C. E., Gonzalez, L., Berzin, T. M., Tavares, R., Hulette, C. M., Vitek, M. P., Hovanesian, V., & Stopa, E. G. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.05.016 · Cited by 487 · see citing works
Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss
Nikolakopoulou, A. M., Montagne, A., Kisler, K., Dai, Z., Wang, Y., Huuskonen, M. T., Sagare, A. P., Lazić, D., Sweeney, M. D., Kong, P., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0434-z · Cited by 382 · see citing works
Self-citationBennett, R. E., Robbins, A. B., Hu, M., Cao, X., Betensky, R. A., Clark, T., Das, S., & Hyman, B. T. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1710329115 · Cited by 299 · see citing works
Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later
Roe, C. M., Fagan, A. M., Grant, E. A., Hassenstab, J., Moulder, K. L., Maue Dreyfus, D., Sutphen, C. L., Benzinger, T. L. S., Mintun, M. A., Holtzman, D. M., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e3182918ca6 · Cited by 222 · see citing works
Self-citationNeurovascular unit impairment in early Alzheimer's disease measured with magnetic resonance imaging
van de Haar, H. J., Jansen, J. F. A., van Osch, M. J. P., van Buchem, M. A., Muller, M., Wong, S. M., Hofman, P. A. M., Burgmans, S., Verhey, F. R. J., & Backes, W. H. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.06.006 · Cited by 207 · see citing works
Hultman, K., Strickland, S., & Norris, E. H. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.76 · Cited by 183 · see citing works
AV-1451 PET imaging of tau pathology in preclinical Alzheimer disease: Defining a summary measure
Mishra, S., Gordon, B. A., Su, Y., Christensen, J. J., Friedrichsen, K. A., Jackson, K., Hornbeck, R. C., Balota, D. A., Cairns, N. J., Morris, J. C., et al. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.07.050 · Cited by 176 · see citing works
Self-citationJak, A. J., Preis, S. R., Beiser, A., Seshadri, S. S., Wolf, P. A., Bondi, M. W., & Au, R. (2016) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617716000199 · Cited by 147 · see citing works
Shedding of soluble platelet-derived growth factor receptor-β from human brain pericytes
Sagare, A. P., Sweeney, M. D., Makshanoff, J., & Zlokovic, B. V. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.09.025 · Cited by 142 · see citing works
Self-citationMiners, J. S., Kehoe, P. G., Love, S., Zetterberg, H., & Blennow, K. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0534-8 · Cited by 137 · see citing works
Neuroimaging Study Designs, Computational Analyses and Data Provenance Using the LONI Pipeline
Dinov, I. D., Lozev, K., Petrosyan, P., Liu, Z., Eggert, P., Pierce, J., Zamanyan, A., Chakrapani, S., Horn, J. D. V., Parker, D. S., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013070 · Cited by 136 · see citing works
Self-citationLessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson’s case.
Marquié, M., Verwer, E. E., Meltzer, A. C., Kim, S. J. W., Agüero, C., Gonzalez, J., Makaretz, S. J., Siao Tick Chong, M., Ramanan, P., Amaral, A. C., et al. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0482-0 · Cited by 128 · see citing works
Brain and Bannister's Clinical Neurology, 7th Ed.
Cole, M. (1993) · Neurology · doi:10.1212/wnl.43.1_part_1.241-a · Cited by 126 · see citing works
Farrer, L. A. (1997) · JAMA · doi:10.1001/jama.1997.03550160069041 · Cited by 124 · see citing works
Faal, T., Phan, D. T. T., Davtyan, H., Scarfone, V. M., Varady, E., Blurton-Jones, M., Hughes, C. C. W., & Inlay, M. A. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.01.005 · Cited by 124 · see citing works
Bangen, K. J., Nation, D. A., Delano‐Wood, L., Weissberger, G. H., Hansen, L. A., Galasko, D. R., Salmon, D. P., & Bondi, M. W. (2014) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.12.025 · Cited by 115 · see citing works
Self-citationEffect of APOE genotype on microvascular basement membrane in Alzheimer's disease
Salloway, S., Gur, T., Berzin, T., Zipser, B., Correia, S., Hovanesian, V, Fallon, J., Kuo-Leblanc, V, Glass, D., Hulette, C., et al. (2002) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(02)00288-5 · Cited by 113 · see citing works
Neuroanatomical morphometric characterization of sex differences in youth using statistical learning
Sepehrband, F., Lynch, K. M., Cabeen, R. P., González-Zacarías, C., Zhao, L., D'Arcy, M., Kesselman, C., Herting, M., Dinov, I., Toga, A., et al. (2018) · NeuroImage · doi:10.1016/j.neuroimage.2018.01.065 · Cited by 90 · see citing works
Self-citationImaging Brain Effects of APOE4 in Cognitively Normal Individuals Across the Lifespan
Fouquet, M., Besson, F. L., Gonneaud, J., Joie, R. L., & Chételat, G. (2014) · Neuropsychology Review · doi:10.1007/s11065-014-9263-8 · Cited by 83 · see citing works
Optimal Reference Region to Measure Longitudinal Amyloid-β Change with 18F-Florbetaben PET
Bullich, S., Villemagne, V. L., Catafau, A. M., Jovalekic, A., Koglin, N., Rowe, C. C., & Santi, S. D. (2017) · Journal of Nuclear Medicine · doi:10.2967/jnumed.116.187351 · Cited by 66 · see citing works
Widespread distribution of tauopathy in preclinical Alzheimer's disease
Schultz, S. A., Gordon, B. A., Mishra, S., Su, Y., Perrin, R. J., Cairns, N. J., Morris, J. C., Ances, B. M., & Benzinger, T. L. S. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.08.022 · Cited by 63 · see citing works
Self-citationNation, D. A., Delano‐Wood, L., Bangen, K. J., Wierenga, C. E., Jak, A. J., Hansen, L. A., Galasko, D. R., Salmon, D. P., & Bondi, M. W. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-111697 · Cited by 49 · see citing works
Self-citationPan, C., Korff, A., Galasko, D. R., Ginghină, C., Peskind, E. R., Li, G., Quinn, J. F., Montine, T. J., Cain, K. C., Shi, M. Y., et al. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-143099 · Cited by 36 · see citing works
Efficacy and safety of alisporivir for the treatment of hepatitis C infection
Stanciu, C., Trifan, A. V., Muzica, C. M., et al. (2018) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2018.1560424 · Cited by 36 · see citing works
Montagne, A., Huuskonen, M. T., Rajagopal, G., Sweeney, M. D., Nation, D. A., Sepehrband, F., D’Orazio, L. M., Harrington, M. G., Chui, H. C., Law, M., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.07.012 · Cited by 33 · see citing works
Self-citationCholesterol and matrisome pathways dysregulated in human APOE ε4 gliaPreprint
Julia, T. C. W., Liang, S., Lü, Q., Pipalia, N. H., Chao, M. J., Shi, Y., Bertelsen, S. E., Kapoor, M., Marcora, E. M., Sikora, E., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/713362 · Cited by 28 · see citing works
Self-citationHigh-resolution intersubject averaging and a coordinate system for the cortical surface
Fischl, B., Sereno, M. I., Tootell, R. B. H., & Dale, A. M. (1999) · Human Brain Mapping · doi:10.1002/(sici)1097-0193(1999)8:4
Flagged first, then by citations
Research works printed but not linked: 1
- [49]Cabeen RP, Laidlaw DH & Toga AW Quantitative imaging toolkit: Software for interactive 3D visualization, data exploration, and computational analysis of neuroimaging datasets. in Proceedings of the International Society for Magnetic Resonance in Medicine (ISMRM) vol. 2854 (2018).
Cited by
Sorted by citations
Scheltens, P., De Strooper, B., Kivipelto, M., Holstege, H., Chételat, G., Teunissen, C. E., Cummings, J., & van der Flier, W. M. (2021) · The Lancet · doi:10.1016/s0140-6736(20)32205-4 · Cited by 5,465 · see citing works
Role of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668 · see citing works
“APOE4 even induces cognitive decline independent of Aβ or tau pathology probably through CypA-MMP9 pathway.(185) In line with the vital role of APOE4 mediate inflammation in the progression of AD, recent epidemiological data suggest that APOE4 carriers response better to NSAIDs treatment.”
BackgroundMicrobiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
APOE and Alzheimer’s disease: Advances in genetics, pathophysiology, and therapeutic approaches
Serrano-Pozo, A., Das, S., & Hyman, B. T. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30412-9 · Cited by 1,037 · see citing works
A human brain vascular atlas reveals diverse mediators of Alzheimer’s risk
Yang, A. C., Vest, R. T., Kern, F., Lee, D. P., Agam, M., Maat, C. A., Losada, P. M., Chen, M. B., Schaum, N., Khoury, N., et al. (2022) · Nature · doi:10.1038/s41586-021-04369-3 · Cited by 797 · see citing works
ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies
Raulin, A.-C., Doss, S. V., Trottier, Z. A., Ikezu, T. C., Bu, G., & Liu, C.-C. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00574-4 · Cited by 756 · see citing works
The blood-brain barrier in aging and neurodegeneration
Knox, E. G., Aburto, M. R., Clarke, G., Cryan, J. F., & O’Driscoll, C. M. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01511-z · Cited by 738 · see citing works
“In this context, carriers of apolipoprotein 4 (APOE4) allele, a major risk factor for AD, present with pericyte degeneration and associated BBB breakdown [42], which has been recently associated with cognitive decline, independent of AD pathology [43].”
BackgroundAPOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia
Haney, M. S., Pálovics, R., Munson, C. N., Long, C., Johansson, P. K., Yip, O., Dong, W., Rawat, E., West, E., Schlachetzki, J. C. M., et al. (2024) · Nature · doi:10.1038/s41586-024-07185-7 · Cited by 536 · see citing works
“Whereas recent studies have focused on the role of APOE in astrocytes 31 , endothelial cells 32 , neurons 33 and oligodendrocytes 34 , the LDAM expression signature, such as ACSL1 and NAMPT upregulation, seems to be unique to microglia.”
Self-citationThe probabilistic model of Alzheimer disease: the amyloid hypothesis revised
Frisoni, G. B., Altomare, D., Thal, D. R., Ribaldi, F., van der Kant, R., Ossenkoppele, R., Blennow, K., Cummings, J., van Duijn, C., Nilsson, P. M., et al. (2022) · Nature Reviews Neuroscience · doi:10.1038/s41583-021-00533-w · Cited by 513 · see citing works
López-Otín, C., & Kroemer, G. (2021) · Cell · doi:10.1016/j.cell.2020.11.034 · Cited by 499 · see citing works
Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy
Da Mesquita, S., Papadopoulos, Z., Dykstra, T., Brase, L., Farias, F. G., Wall, M., Jiang, H., Kodira, C. D., de Lima, K. A., Herz, J., et al. (2021) · Nature · doi:10.1038/s41586-021-03489-0 · Cited by 431 · see citing works
Cholesterol and matrisome pathways dysregulated in astrocytes and microglia
TCW, J., Qian, L., Pipalia, N. H., Chao, M. J., Liang, S. A., Shi, Y., Jain, B. R., Bertelsen, S. E., Kapoor, M., Marcora, E., et al. (2022) · Cell · doi:10.1016/j.cell.2022.05.017 · Cited by 411 · see citing works
Self-citationWang, C., Xiong, M., Gratuze, M., Bao, X., Shi, Y., Andhey, P. S., Manis, M., Schroeder, C., Yin, Z., Madore, C., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.03.024 · Cited by 334 · see citing works
Emerging roles of innate and adaptive immunity in Alzheimer’s disease
Chen, X., & Holtzman, D. M. (2022) · Immunity · doi:10.1016/j.immuni.2022.10.016 · Cited by 297 · see citing works
Challenges and hopes for Alzheimer’s disease
Tatulian, S. A. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.01.016 · Cited by 291 · see citing works
Blood–Brain Barrier Breakdown in Alzheimer’s Disease: Mechanisms and Targeted Strategies
Alkhalifa, A. E., Al-Ghraiybah, N. F., Odum, J., Shunnarah, J. G., Austin, N., & Kaddoumi, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216288 · Cited by 212 · see citing works
Modeling Sporadic Alzheimer's Disease in Human Brain Organoids under Serum Exposure
Chen, X., Sun, G., Tian, E., Zhang, M., Davtyan, H., Beach, T. G., Reiman, E. M., Blurton‐Jones, M., Holtzman, D. M., & Shi, Y. (2021) · Advanced Science · doi:10.1002/advs.202101462 · Cited by 200 · see citing works
Self-citationMultifaceted roles of APOE in Alzheimer disease
Jackson, R. J., Hyman, B. T., & Serrano-Pozo, A. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-00988-2 · Cited by 193 · see citing works
Dysfunction of the blood–brain barrier in Alzheimer's disease: Evidence from human studies
Kurz, C., Walker, L., Rauchmann, B., & Perneczky, R. (2022) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12782 · Cited by 183 · see citing works
“reported to emerge independently of tau and Aβ amyloid pathology.(96)”
BackgroundThe use of neuroimaging techniques in the early and differential diagnosis of dementia
Chouliaras, L., & O’Brien, J. T. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02215-8 · Cited by 186 · see citing works
“In a follow up study, BBB breakdown in the hippocampus and medial temporal lobe was able to distinguish Apolipoprotein (APOE) ε 4 from non-ε 4 carriers [75].”
BackgroundAntiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
Jiang, Q., Liu, J., Huang, S., Wang, X.-Y., Chen, X., Liu, G.-H., Ye, K., Song, W., Masters, C. L., Wang, J., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02145-7 · Cited by 165 · see citing works
Biomarkers used in Alzheimer’s disease diagnosis, treatment, and prevention
Mahaman, Y. A. R., Embaye, K. S., Huang, F., Li, L., Zhu, F., Wang, J.-Z., Liu, R., Feng, J., & Wang, X. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101544 · Cited by 149 · see citing works
Blood-brain barrier leakage in Alzheimer’s disease: From discovery to clinical relevance
Nehra, G., Bauer, B., & Hartz, A. M. S. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108119 · Cited by 127 · see citing works
Defining blood-induced microglia functions in neurodegeneration through multiomic profiling
Mendiola, A. S., Yan, Z., Dixit, K., Johnson, J. R., Bouhaddou, M., Meyer-Franke, A., Shin, M.-G., Yong, Y., Agrawal, A., MacDonald, E., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01522-0 · Cited by 124 · see citing works
Bateman, R. J., Cummings, J., Schobel, S., Salloway, S., Vellas, B., Boada, M., Black, S. E., Blennow, K., Fontoura, P., Klein, G., et al. (2022) · Alzheimer's Research & Therapy · doi:10.1186/s13195-022-01110-8 · Cited by 109 · see citing works
Interplay between Brain Pericytes and Endothelial Cells in Dementia
Procter, T. V., Williams, A., & Montagne, A. (2021) · The American Journal of Pathology · doi:10.1016/j.ajpath.2021.07.003 · Cited by 106 · see citing works
Self-citationAstrocytes in the regulation of cerebrovascular functions
Cohen‐Salmon, M., Slaoui, L., Mazaré, N., Gilbert, A., Oudart, M., Alvear‐Perez, R., Elorza‐Vidal, X., Chever, O., & Boulay, A. (2021) · Glia · doi:10.1002/glia.23924 · Cited by 93 · see citing works
Tsartsalis, S., Sleven, H., Fancy, N., Wessely, F., Smith, A. M., Willumsen, N., Cheung, T. K. D., Rokicki, M. J., Chau, V., Ifie, E., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46630-z · Cited by 95 · see citing works
Self-citationLitvinchuk, A., Huynh, T. V., Shi, Y., Jackson, R. J., Finn, M. B., Manis, M., Francis, C. M., Tran, A. C., Sullivan, P. M., Ulrich, J. D., et al. (2021) · Annals of Neurology · doi:10.1002/ana.26043 · Cited by 91 · see citing works
APOE2 is associated with longevity independent of Alzheimer’s disease
Shinohara, M., Kanekiyo, T., Tachibana, M., Kurti, A., Shinohara, M., Fu, Y., Zhao, J., Han, X., Sullivan, P. M., Rebeck, G. W., et al. (2020) · eLife · doi:10.7554/elife.62199 · Cited by 82 · see citing works
Cerebrovascular Senescence Is Associated With Tau Pathology in Alzheimer's Disease
Bryant, A. G., Hu, M., Carlyle, B. C., Arnold, S. E., Frosch, M. P., Das, S., Hyman, B. T., & Bennett, R. E. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.575953 · Cited by 79 · see citing works
Jeon, M.-T., Kim, K.-S., Kim, E. S., Lee, S., Kim, J., Hoe, H.-S., & Kim, D.-G. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101333 · Cited by 76 · see citing works
APOE effects on regional tau in preclinical Alzheimer’s disease
Young, C. B., Johns, E., Kennedy, G., Belloy, M. E., Insel, P. S., Greicius, M. D., Sperling, R. A., Johnson, K. A., Poston, K. L., Mormino, E. C., et al. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00590-4 · Cited by 80 · see citing works
Anti-amyloid-β protein agents for the treatment of Alzheimer’s disease: an update on emerging drugs
Lozupone, M., Solfrizzi, V., D’Urso, F., Di Gioia, I., Sardone, R., Dibello, V., Stallone, R., Liguori, A., Ciritella, C., Daniele, A., et al. (2020) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2020.1808621 · Cited by 77 · see citing works
Astrocyte-secreted glypican-4 drives APOE4-dependent tau hyperphosphorylation
Saroja, S. R., Gorbachev, K., Julia, T., Goate, A. M., & Pereira, A. C. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2108870119 · Cited by 75 · see citing works
Qian, J., Betensky, R. A., Hyman, B. T., & Serrano-Pozo, A. (2021) · Neurology · doi:10.1212/wnl.0000000000011883 · Cited by 71 · see citing works
Blood cell-produced amyloid-β induces cerebral Alzheimer-type pathologies and behavioral deficits
Sun, H.-L., Chen, S.-H., Yu, Z.-Y., Cheng, Y., Tian, D.-Y., Fan, D.-Y., He, C.-Y., Wang, J., Sun, P.-Y., Chen, Y., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-0842-1 · Cited by 56 · see citing works
Self-citationApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease
Li, Y., Macyczko, J. R., Liu, C.-C., & Bu, G. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.03.011 · Cited by 61 · see citing works
Effects of APOE4 allelic dosage on lipidomic signatures in the entorhinal cortex of aged mice
Miranda, A. M., Ashok, A., Chan, R. B., Zhou, B., Xu, Y., McIntire, L. B., Area-Gomez, E., Di Paolo, G., Duff, K. E., Oliveira, T. G., et al. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01881-6 · Cited by 60 · see citing works
“Indeed, aging has been shown to be associated with blood brain barrier (BBB) breakdown in the hippocampus [93], and BBB leakage is also found to be an early marker of dysfunction in both APOE4 carriers [94] and mice [95].”
BackgroundA New Hypothesis for Alzheimer’s Disease: The Lipid Invasion Model
Rudge, J. D. (2022) · Journal of Alzheimer's Disease Reports · doi:10.3233/adr-210299 · Cited by 58 · see citing works
Impact of COVID-19 on Alzheimer’s Disease Risk: Viewpoint for Research Action
Abate, G., Memo, M., & Uberti, D. (2020) · Healthcare · doi:10.3390/healthcare8030286 · Cited by 56 · see citing works
Zhao, Q., Dai, W., Chen, H. Y., Jacobs, R. E., Zlokovic, B. V., Lund, B. T., Montagne, A., & Bonnin, A. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2113310119 · Cited by 52 · see citing works
Self-citationA human brain vascular atlas reveals diverse cell mediators of Alzheimer’s disease risk
Yang, A. C., Vest, R. T., Kern, F., Lee, D. P., Maat, C. A., Losada, P. M., Chen, M. B., Agam, M., Schaum, N., Khoury, N., et al. (2021) · doi:10.1101/2021.04.26.441262 · Cited by 48 · see citing works
Omega-3 fatty acids are associated with blood-brain barrier integrity in a healthy aging population
Barnes, S., Chowdhury, S., Gatto, N. M., Fraser, G. E., & Lee, G. J. (2021) · Brain and Behavior · doi:10.1002/brb3.2273 · Cited by 47 · see citing works
Jana, A., Wang, X., Leasure, J. W., Magana, L., Wang, L., Kim, Y.-M., Dodiya, H., Toth, P. T., Sisodia, S. S., & Rehman, J. (2022) · Scientific Reports · doi:10.1038/s41598-022-20889-y · Cited by 43 · see citing works
Albrecht, D. S., Sagare, A., Pachicano, M., Sweeney, M. D., Toga, A., Zlokovic, B., Chui, H., Joe, E., Schneider, L., Morris, J. C., et al. (2021) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2021.01.010 · Cited by 37 · see citing works
Self-citationUse of Donanemab in Early Symptomatic Alzheimer Disease—Reply
Evans, C. D., & Sims, J. R. (2023) · JAMA · doi:10.1001/jama.2023.21109 · Cited by 35 · see citing works
Kloske, C. M., Belloy, M. E., Blue, E. E., Bowman, G. R., Carrillo, M. C., Chen, X., Chiba‐Falek, O., Davis, A. A., Paolo, G. D., Garretti, F., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13877 · Cited by 33 · see citing works
Self-citationJiang, Y., Uhm, H., Ip, F. C., Ouyang, L., Lo, R. M. N., Cheng, E. Y. L., Cao, X., Tan, C. M. C., Law, B. C. H., Ortiz‐Romero, P., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13676 · Cited by 36 · see citing works
The aged hematopoietic system promotes hippocampal‐dependent cognitive decline
Smith, L. K., Verovskaya, E., Bieri, G., Horowitz, A. M., von Ungern‐Sternberg, S. N. I., Lin, K., Seizer, P., Passegué, E., & Villeda, S. A. (2020) · Aging Cell · doi:10.1111/acel.13192 · Cited by 31 · see citing works
Preman, P., Moechars, D., Fertan, E., Wolfs, L., Serneels, L., Shah, D., Lamote, J., Poovathingal, S., Snellinx, A., Mancuso, R., et al. (2024) · EMBO Molecular Medicine · doi:10.1038/s44321-024-00162-7 · Cited by 32 · see citing works
Botchway, B. O., Okoye, F. C., Chen, Y., Arthur, W. E., & Fang, M. (2022) · Aging and disease · doi:10.14336/ad.2021.0616 · Cited by 32 · see citing works
Self-citationTarawneh, R. (2023) · Biomolecules · doi:10.3390/biom13050830 · Cited by 29 · see citing works
Newton, P., the BIOCARD Research Team, Tchounguen, J., Pettigrew, C., Lim, C., Lin, Z., Lu, H., Moghekar, A., Albert, M., & Soldan, A. (2023) · Journal of Alzheimer's Disease · doi:10.3233/jad-220846 · Cited by 23 · see citing works
Evidence of beta amyloid independent small vessel disease in familial Alzheimer's disease
Littau, J. L., Velilla, L., Hase, Y., Villalba‐Moreno, N. D., Hagel, C., Drexler, D., Osorio Restrepo, S., Villegas, A., Lopera, F., Vargas, S., et al. (2022) · Brain Pathology · doi:10.1111/bpa.13097 · Cited by 20 · see citing works
Li, X., Tang, X., Zeng, J., Duan, L., Hou, Z., Li, L., Guo, Y., Chai, C., Liu, J., Wang, Y., et al. (2026) · Cell · doi:10.1016/j.cell.2025.12.020 · Cited by 21 · see citing works
Pathogenesis, Animal Models, and Drug Discovery of Alzheimer’s Disease
Xia, Z.-D., Ma, R.-X., Wen, J.-F., Zhai, Y.-F., Wang, Y.-Q., Wang, F.-Y., Liu, D., Zhao, X.-L., Sun, B., Jia, P., et al. (2023) · Journal of Alzheimer's Disease · doi:10.3233/jad-230326 · Cited by 19 · see citing works
Zhang, Q., Song, Q., Gu, X., Zheng, M., Wang, A., Jiang, G., Huang, M., Chen, H., Qiu, Y., Bo, B., et al. (2021) · Advanced Science · doi:10.1002/advs.202001918 · Cited by 19 · see citing works
Huang, A. Y., Zhou, Z., Talukdar, M., Enyenihi, L., Miller, M. B., Chhouk, B., Rosen, I., Zheng, M., Zhou, M., Yang, A., et al. (2026) · Cell · doi:10.1016/j.cell.2026.03.040 · Cited by 15 · see citing works
Yin, H., Lu, Z., Deng, Y., Tian, X., & Gong, Q. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102952 · Cited by 6 · see citing works
APOE4-drives brain bioenergetic shifts independent of Alzheimer’s disease pathology
Lysaker, C. R., Johnson, C. N., Csikos, V., Franczak, E., Benson, M., Gilmore, C. A., Birky, C. J., Davis, X., McCoin, C. S., Smith, K. P., et al. (2026) · npj Dementia · doi:10.1038/s44400-026-00105-8 · Cited by 1 · see citing works
Self-citationChen, K., Chen, Y., Ren, Y., Wang, Z., Huang, Y., Pan, M., Li, Z., Casey, M. C., Qiao, W., Shi, J., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-78407-x
Self-citation
- Authors
- Montagne, A., Nation, D. A., Sagare, A. P., Barisano, G., Sweeney, M. D., Chakhoyan, A., Pachicano, M., Joe, E., Nelson, A. R., D’Orazio, L. M., Buennagel, D. P., Harrington, M. G., Benzinger, T. L. S., Fagan, A. M., Ringman, J. M., Schneider, L. S., Morris, J. C., Reiman, E. M., Caselli, R. J., Chui, H. C., TCW, J., Chen, Y., Pa, J., Conti, P. S., Law, M., Toga, A. W., & Zlokovic, B. V.
- Affiliations
- University of Southern California (US)
- Huntington Medical Research Institutes (US)
- Washington University in St. Louis (US)
- Banner Alzheimer’s Institute (US)
- Mayo Clinic (US)
- Icahn School of Medicine at Mount Sinai (US)
- ORCID
- Montagne, Axel
- Nation, Daniel A.
- Sagare, Abhay P.
- Barisano, Giuseppe
- Sweeney, Melanie D.
- Chakhoyan, Ararat
- Pachicano, Maricarmen
- Joe, Elizabeth
- Nelson, Amy R.
- Harrington, Michael G.
- Benzinger, Tammie L. S.
- Fagan, Anne M.
- Ringman, John M.
- Schneider, Lon S.
- Morris, John C.
- Reiman, Eric M.
- Caselli, Richard J.
- Chui, Helena C.
- TCW, Julia
- Chen, Yining
- Pa, Judy
- Conti, Peter S.
- Law, Meng
- Toga, Arthur W.
- Zlokovic, Berislav V.
- Venue
- Nature
- Published
- 2020-04-29
- Volume
- 581
- Issue
- 7806
- Pages
- 71-76
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7250000
- OpenAlex
- W3022539327
- Cited by
- 1,281
- References
- 57
- Citations by year
- 2026: 190 · 2025: 174 · 2024: 196 · 2023: 208 · 2022: 198 · 2021: 218 · 2020: 95 · 2019: 1
- FWCI
- 69.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Alzheimer's Association (509279, AARG-17-532905)
- Eli Lilly and Company
- Cure Alzheimer's Fund (16 CVD 05)
- National Institutes of Health (509279, UL1TR002345)
- Avid Radiopharmaceuticals
- Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. Louis (P50 AG0568 1, P01AG03991, P01AG026276)
- National Institute on Aging (P30-AG-19610, R01AG023084, R01AG039452, R01AG055770, R01AG060049, AARG-17-532905, P50AG016573, K01AG062683, P 50 AG05681, R01AG031581, P50AG005681, P50AG005142, K99AG058780, P30AG019610, P01 AG0 3991, P01AG003991, R00AG058780, R01AG054434, R01AG064228, P01AG052350, P30AG066444, P30AG066530, P01AG026276)
- National Institute of Neurological Disorders and Stroke (R01NS100459, R01NS090904, R01NS034467)
- National Institute of Biomedical Imaging and Bioengineering (R01EB009352)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- APOE ε4, blood-brain barrier disruption, cognitive decline, Alzheimer's disease, cyclophilin A, MMP-9, cerebrovascular dysfunction, hippocampus, medial temporal lobe, amyloid-beta, tau pathology, cerebrospinal fluid biomarkers, vascular dementia
- MeSH terms
- Alleles, Alzheimer Disease, Blood-Brain Barrier, Capillaries, Female, Heterozygote, Hippocampus, Humans, Male, Temporal Lobe, Amyloid beta-Peptides, tau Proteins, Pericytes, Parahippocampal Gyrus, Matrix Metalloproteinase 9, Receptor, Platelet-Derived Growth Factor beta, Cyclophilin A, Positron-Emission Tomography, Apolipoprotein E4, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
