Selective loss of cortical endothelial tight junction proteins during Alzheimer’s disease progression
Open accessAbstract
While the accumulation and aggregation of amyloid-β and tau are central events in the pathogenesis of Alzheimer’s disease, there is increasing evidence that cerebrovascular pathology is also abundant in Alzheimer’s disease brains. In brain capillaries, endothelial cells are connected closely with one another through transmembrane tight junction proteins forming the blood–brain barrier. Because the blood–brain barrier tightly regulates the exchange of molecules between brain and blood and maintains brain homeostasis, its impairment is increasingly recognized as a critical factor contributing to Alzheimer’s disease pathogenesis. However, the pathological relationship between blood–brain barrier properties and Alzheimer’s disease progression in the human brain is not fully understood. In this study, we show that the loss of cortical tight junction proteins is a common event in Alzheimer’s disease, and is correlated with synaptic degeneration. By quantifying the amounts of major tight junction proteins, claudin-5 and occludin, in 12 brain regions dissected from post-mortem brains of normal ageing (n = 10), pathological ageing (n = 14) and Alzheimer’s disease patients (n = 19), we found that they were selectively decreased in cortical areas in Alzheimer’s disease. Cortical tight junction proteins were decreased in association with the Braak neurofibrillary tangle stage. There was also a negative correlation between the amount of tight junction proteins and the amounts of insoluble Alzheimer’s disease-related proteins, in particular amyloid-β40, in cortical areas. In addition, the amount of tight junction proteins in these areas correlated positively with those of synaptic markers. Thus, loss of cortical tight junction proteins in Alzheimer’s disease is associated with insoluble amyloid-β40 and loss of synaptic markers. Importantly, the positive correlation between claudin-5 and synaptic markers, in particular synaptophysin, was present independent of insoluble amyloid-β40, amyloid-β42 and tau values, suggesting that loss of cortical tight junction proteins and synaptic degeneration is present, at least in part, independent of insoluble Alzheimer’s disease-related proteins. Collectively, these results indicate that loss of tight junction proteins occurs predominantly in the neocortex during Alzheimer’s disease progression. Further, our findings provide a neuropathological clue as to how endothelial tight junction pathology may contribute to Alzheimer’s disease pathogenesis in both synergistic and additive manners to typical amyloid-β and tau pathologies.
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?
Ezr and Cldn5 are associated with maintenance of actin cytoskeletal structure, synapse and tight junctions, respectively.
“Interestingly, long term infection also induced expressions of Ezr91 and Cldn592 which are associated with maintenance of actin cytoskeletal structure, synapse and tight junctions, respectively.”
From Chlamydia pneumoniae can infect the central nervous system via the olfactory and trigeminal nerves and contributes to Alzheimer’s disease risk (2022) · cites this paper as [92]
Long-term infection induced expressions of Ezr and Cldn5.
“Interestingly, long term infection also induced expressions of Ezr91 and Cldn592 which are associated with maintenance of actin cytoskeletal structure, synapse and tight junctions, respectively.”
From Chlamydia pneumoniae can infect the central nervous system via the olfactory and trigeminal nerves and contributes to Alzheimer’s disease risk (2022) · cites this paper as [92]
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
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Neuropathological alterations in Alzheimer disease
Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006189 · Cited by 3,345 · see citing works
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280 · see citing works
Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
Zlokovic, B. V. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3114 · Cited by 2,969 · see citing works
Buckner, R. L., Snyder, A. Z., Shannon, B. J., LaRossa, G., Sachs, R., Fotenos, A. F., Sheline, Y. I., Klunk, W. E., Mathis, C. A., Morris, J. C., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2177-05.2005 · Cited by 2,140 · 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
Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., et al. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31825018f7 · Cited by 2,050 · see citing works
Alzheimer's disease: experimental models and reality
Drummond, E., & Wisniewski, T. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1662-x · Cited by 810 · see citing works
GLUT1 reductions exacerbate Alzheimer's disease vasculo-neuronal dysfunction and degeneration
Winkler, E. A., Nishida, Y., Sagare, A. P., Rege, S. V., Bell, R. D., Perlmutter, D., Sengillo, J. D., Hillman, S., Kong, P., Nelson, A. R., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.3966 · Cited by 689 · see citing works
Cirrito, J. R. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25247 · Cited by 660 · see citing works
Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease
Erickson, M. A., & Banks, W. A. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.135 · Cited by 572 · see citing works
Endothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier
Storck, S. E., Meister, S., Nahrath, J., Meißner, J. N., Schubert, N., Di Spiezio, A., Baches, S., Vandenbroucke, R. E., Bouter, Y., Prikulis, I., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci81108 · Cited by 477 · see citing works
Spatial correlation between brain aerobic glycolysis and amyloid-β (Aβ) deposition
Vlassenko, A. G., Vaishnavi, S. N., Couture, L., Sacco, D., Shannon, B. J., Mach, R. H., Morris, J. C., Raichle, M. E., & Mintun, M. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010461107 · Cited by 404 · see citing works
Synaptic slaughter in Alzheimer's disease
Coleman, P. (2003) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.09.001 · Cited by 351 · see citing works
Carrano, A., Hoozemans, J. J. M., van der Vies, S. M., Rozemuller, A. J. M., van Horssen, J., & de Vries, H. E. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.3895 · Cited by 293 · see citing works
Vascular Cell Senescence Contributes to Blood–Brain Barrier Breakdown
Yamazaki, Y., Baker, D. J., Tachibana, M., Liu, C.-C., van Deursen, J. M., Brott, T. G., Bu, G., & Kanekiyo, T. (2016) · Stroke · doi:10.1161/strokeaha.115.010835 · Cited by 263 · see citing works
Self-citationMiners, J. S., Schulz, I., & Love, S. (2018) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17690761 · Cited by 208 · see citing works
Neuroinflammation and blood-brain barrier changes in capillary amyloid angiopathy
Carrano, A., Hoozemans, J. J. M., van der Vies, S. M., van Horssen, J., de Vries, H. E., & Rozemuller, A. J. M. (2012) · Neurodegenerative Diseases · doi:10.1159/000334916 · Cited by 186 · see citing works
Wiring the Vascular Network with Neural Cues: A CNS Perspective
Wälchli, T., Wacker, A., Frei, K., Regli, L., Schwab, M. E., Hoerstrup, S. P., Gerhardt, H., & Engelhardt, B. (2015) · Neuron · doi:10.1016/j.neuron.2015.06.038 · Cited by 178 · see citing works
Shinohara, M., Fujioka, S., Murray, M. E., Wojtas, A., Baker, M., Rovelet-Lecrux, A., Rademakers, R., Das, P., Parisi, J. E., Graff-Radford, N. R., et al. (2014) · Brain · doi:10.1093/brain/awu046 · Cited by 115 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 43
- Arvanitakis Z, Capuano AW, Leurgans SE, Bennett DA, Schneider JA. Relation of cerebral vessel disease to Alzheimer's disease dementia and cognitive function in elderly people: a cross-sectional study. Lancet Neurol 2016; 15: 934-43.
- Banerjee G, Kim HJ, Fox Z, Jager HR, Wilson D, Charidimou A, et al. MRI-visible perivascular space location is associated with Alzheimer's disease independently of amyloid burden. Brain 2017; 140: 1107-16.
- Bayer TA, Wirths O. Focusing the amyloid cascade hypothesis on N- truncated Abeta peptides as drug targets against Alzheimer's disease. Acta Neuropathol 2014; 127: 787-801.
- Bennett RE, Robbins AB, Hu M, Cao X, Betensky RA, Clark T, et al. Tau induces blood vessel abnormalities and angiogenesis-related gene expression in P301L transgenic mice and human Alzheimer's disease. Proc Natl Acad Sci USA 2018; 115: E1289-98.
- Craggs LJ, Hagel C, Kuhlenbaeumer G, Borjesson-Hanson A, Andersen O, Viitanen M, et al. Quantitative vascular pathology and phenotyping familial and sporadic cerebral small vessel diseases. Brain Pathol 2013; 23: 547-57.
- Daneman R. The blood-brain barrier in health and disease. Ann Neurol 2012; 72: 648-72.
- Daneman R, Prat A. The blood-brain barrier. Cold Spring Harb Perspect Biol 2015; 7: a020412.
- Deane R, Wu Z, Sagare A, Davis J, Du Yan S, Hamm K, et al. LRP/ amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms. Neuron 2004; 43: 333-44.
- Deeken JF, Loscher W. The blood-brain barrier and cancer: trans- porters, treatment, and Trojan horses. Clin Cancer Res 2007; 13: 1663-74.
- DeKosky ST, Scheff SW, Styren SD. Structural correlates of cognition in dementia: quantification and assessment of synapse change. Neurodegeneration 1996; 5: 417-21.
- Dickson DW, Crystal HA, Mattiace LA, Masur DM, Blau AD, Davies P, et al. Identification of normal and pathological aging in prospect- ively studied nondemented elderly humans. Neurobiol Aging 1992; 13: 179-89.
- Dolan H, Crain B, Troncoso J, Resnick SM, Zonderman AB, Obrien RJ. Atherosclerosis, dementia, and Alzheimer disease in the Baltimore Longitudinal Study of Aging cohort. Ann Neurol 2010; 68: 231-40.
- Harik SI. Changes in the glucose transporter of brain capillaries. Can J Physiol Pharm 1992; 70: S113-7.
- Hawkes CA, Gatherer M, Sharp MM, Dorr A, Yuen HM, Kalaria R, et al. Regional differences in the morphological and functional ef- fects of aging on cerebral basement membranes and perivascular drainage of amyloid-beta from the mouse brain. Aging Cell 2013; 12: 224-36.
- Horwood N, Davies DC. Immunolabelling of hippocampal microvessel glucose transporter protein is reduced in Alzheimer's disease. Virchows Arch 1994; 425: 69-72.
- Jack CR, Lowe VJ, Senjem ML, Weigand SD, Kemp BJ, Shiung MM, et al. 11C PiB and structural MRI provide complementary informa- tion in imaging of Alzheimer's disease and amnestic mild cognitive impairment. Brain 2008; 131: 665-80.
- Jankowsky JL, Zheng H. Practical considerations for choosing a mouse model of Alzheimer's disease. Mol Neurodegener 2017; 12: 89. Kapasi A, Schneider JA. Vascular contributions to cognitive impair- ment, clinical Alzheimer's disease, and dementia in older persons. Biochim Biophys Acta 2016; 1862: 878-86.
- Kazmierski R, Michalak S, Wencel-Warot A, Nowinski WL. Serum tight-junction proteins predict hemorrhagic transformation in ische- mic stroke patients. Neurology 2012; 79: 1677-85.
- Keaney J, Walsh DM, O'Malley T, Hudson N, Crosbie DE, Loftus T, et al. Autoregulated paracellular clearance of amyloid-beta across the blood-brain barrier. Sci Adv 2015; 1: e1500472.
- Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol 2004; 55: 306-19.
- Koffie RM, Hyman BT, Spires-Jones TL. Alzheimer's disease: synapses gone cold. Mol Neurodegener 2011; 6: 63.
- Kook SY, Hong HS, Moon M, Ha CM, Chang S, Mook-Jung I. Abeta(1)(-)(4)(2)-RAGE interaction disrupts tight junctions of the blood-brain barrier via Ca(2)( + )-calcineurin signaling. J Neurosci 2012; 32: 8845-54.
- Love S, Chalmers K, Ince P, Esiri M, Attems J, Jellinger K, et al. Development, appraisal, validation and implementation of a con- sensus protocol for the assessment of cerebral amyloid angiopathy in post-mortem brain tissue. Am J Neurodegener Dis 2014; 3: 19- 32.
- Marques F, Sousa JC, Sousa N, Palha JA. Blood-brain-barriers in aging and in Alzheimer's disease. Mol Neurodegener 2013; 8: 38.
- Miller MC, Tavares R, Johanson CE, Hovanesian V, Donahue JE, Gonzalez L, et al. Hippocampal RAGE immunoreactivity in early and advanced Alzheimer's disease. Brain Res 2008; 1230: 273-80.
- Miners JS, Palmer JC, Love S. Pathophysiology of hypoperfusion of the precuneus in early Alzheimer's disease. Brain Pathol 2016; 26: 533-41.
- Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 1991; 41: 479-86.
- Montagne A, Zhao Z, Zlokovic BV. Alzheimer's disease: a matter of blood-brain barrier dysfunction? J Exp Med 2017; 214: 3151-69.
- Mooradian AD, Chung HC, Shah GN. GLUT-1 expression in the cerebra of patients with Alzheimer's disease. Neurobiol Aging 1997; 18: 469-74.
- Murray ME, Dickson DW. Is pathological aging a successful resistance against amyloid-beta or preclinical Alzheimer's disease? Alzheimers Res Ther 2014; 6: 24.
- Ramirez J, McNeely AA, Scott CJM, Masellis M, Black SE. White matter hyperintensity burden in elderly cohort studies: The Sunnybrook Dementia Study, Alzheimer's Disease Neuroimaging Initiative, and Three-City Study. Alzheimers Dement 2016; 12: 203-10.
- Romanitan MO, Popescu BO, Spulber S, Bajenaru O, Popescu LM, Winblad B, et al. Altered expression of claudin family proteins in Alzheimer's disease and vascular dementia brains. J Cell Mol Med 2010; 14: 1088-100.
- Romanitan MO, Popescu BO, Winblad B, Bajenaru OA, Bogdanovic N. Occludin is overexpressed in Alzheimer's disease and vascular dementia. J Cell Mol Med 2007; 11: 569-79.
- Shinohara M, Koga S, Konno T, Nix J, Shinohara M, Aoki N, et al. Distinct spatiotemporal accumulation of N-truncated and full-length amyloid-beta42 in Alzheimer's disease. Brain 2017; 140: 3301-16.
- Shinohara M, Murray ME, Frank RD, DeTure M, Yamazaki Y, Tachibana M, et al. Impact of sex and APOE4 on cerebral amyloid angiopathy in Alzheimer's disease. Acta Neuropathol 2016; 132: 225-34.
- Shinohara M, Petersen RC, Dickson DW, Bu G. Brain regional cor- relation of amyloid-beta with synapses and apolipoprotein E in non- demented individuals: potential mechanisms underlying regional vul- nerability to amyloid-beta accumulation. Acta Neuropathol 2013; 125: 535-47.
- Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, et al. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991; 30: 572-80.
- Wang M, Roussos P, McKenzie A, Zhou X, Kajiwara Y, Brennand KJ, et al. Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective re- gional vulnerability to Alzheimer's disease. Genome Med 2016; 8: 104.
- Yamazaki Y, Kanekiyo T. Blood-brain barrier dysfunction and the pathogenesis of Alzheimer's disease. Int J Mol Sci 2017; 18: 1965.
- Ye BS, Seo SW, Kim GH, Noh Y, Cho H, Yoon CW, et al. Amyloid burden, cerebrovascular disease, brain atrophy, and cognition in cognitively impaired patients. Alzheimers Dement 2015; 11: 494- 503.
- Zenaro E, Piacentino G, Constantin G. The blood-brain barrier in Alzheimer's disease. Neurobiol Dis 2017; 107: 41-56.
- Zhao Z, Nelson AR, Betsholtz C, Zlokovic BV. Establishment and dysfunction of the blood-brain barrier. Cell 2015; 163: 1064-78.
- Zlokovic BV. Neurovascular mechanisms of Alzheimer's neurodegen- eration. Trends Neurosci 2005; 28: 202-8.
Cited by
Sorted by citations
Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C.-C., & Bu, G. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0228-7 · Cited by 1,425 · see citing works
Self-citationThe 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
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
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
“damage and CAA type 1 (capillary type), but not CAA type 2 (noncapillary type).(33,38,53,56) BBB damage (measured by fibrinogen extravasation) correlated with SVD and CAA pathology, and to a lesser degree with cortical AD-related pathology.”
BackgroundInfluentialBlood-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
The relationship between amyloid-beta and brain capillary endothelial cells in Alzheimer’s disease
Su, Q., Guo, J.-H., Zhang, Y.-L., Wang, J., & Zhang, Z.-N. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.335829 · Cited by 91 · see citing works
Yamazaki, Y., Shinohara, M., Yamazaki, A., Ren, Y., Asmann, Y. W., Kanekiyo, T., & Bu, G. (2020) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.119.313169 · Cited by 89 · see citing works
Self-citationCerebrovascular 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
Chacko, A., Delbaz, A., Walkden, H., Basu, S., Armitage, C. W., Eindorf, T., Trim, L. K., Miller, E., West, N. P., St John, J. A., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-06749-9 · Cited by 65 · see citing works
GJ-4 alleviates Aβ25-35-induced memory dysfunction in mice through protecting the neurovascular unit
Zhang, Z., Liu, H., Zhao, Z., Zang, C., Ju, C., Li, F., Wang, L., Yang, H., Bao, X., Yu, Y., et al. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110131 · Cited by 19 · 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
- Authors
- Yamazaki, Y., Shinohara, M., Shinohara, M., Yamazaki, A., Murray, M. E., Liesinger, A. M., Heckman, M. G., Lesser, E. R., Parisi, J. E., Petersen, R. C., Dickson, D. W., Kanekiyo, T., & Bu, G.
- Affiliations
- Mayo Clinic in Florida (US)
- Mayo Clinic (US)
- Corresponding author
- Kanekiyo, Takahisa
- Bu, Guojun
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-02-15
- Volume
- 142
- Issue
- 4
- Pages
- 1077-1092
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC6439325
- OpenAlex
- W2912592608
- Cited by
- 202
- References
- 20
- Citations by year
- 2026: 26 · 2025: 38 · 2024: 27 · 2023: 23 · 2022: 27 · 2021: 30 · 2020: 22 · 2019: 7 · 2015: 1 · 2012: 1
- FWCI
- 9.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- National Institutes of Health
- NIH (RF1AG051504, P50AG016574, R37AG027924, R01AG035355, R01AG046205, U01AG006786, R01AG054449, R01AG051574)
- Cure Alzheimer’s Fund
- GHR Foundation
- American Heart Association (15SDG22460003)
- Florida Department of Health Ed and Ethel Moore
- Alzheimer’s Disease Research (7AZ22)
- Japan Society for the Promotion of Science
- JSPS
- Mochida Memorial Foundation for Medical & Pharmaceutical Research
- Mayo Clinic Alzheimer's Disease Research Center and American Heart Association
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, blood-brain barrier, tight junction proteins, claudin-5, occludin, synaptic degeneration, synaptophysin, Aβ40, cerebrovascular pathology, postmortem brain
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Blood-Brain Barrier, Brain, Female, Humans, Male, Middle Aged, Peptide Fragments, Amyloid beta-Peptides, Neurofibrillary Tangles, tau Proteins, Disease Progression, Tight Junctions, Neocortex, Endothelial Cells, Tight Junction Proteins
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
