The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory
Open accessAbstract
The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer’s disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II–VI. In contrast, the BIN1 rs744373 SNP was not associated with AV45 amyloid-PET uptake. Furthermore, the rs744373 risk-allele was associated with worse memory performance, mediated by increased global tau levels. Together, our findings suggest that the BIN1 rs744373 SNP is associated with increased tau but not beta-amyloid pathology, suggesting that alterations in BIN1 may contribute to memory deficits via increased tau pathology.
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SNPs of BIN1, such as rs744373 and rs7561528, may contribute to AD susceptibility by impacting brain structure and function.
“In addition, the SNPs of BIN1, such as rs744373 and rs7561528, may contribute to AD susceptibility by impacting brain structure and function [480, 481].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [481]
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Lambert, E., Saha, O., Landeira, B. S., de Farias, A. R. M., Hermant, X., Carrier, A., Pelletier, A., Gadaut, J., Davoine, L., Dupont, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.18093090
Lambert, E., Saha, O., Landeira, B. S., de Farias, A. R. M., Hermant, X., Carrier, A., Pelletier, A., Gadaut, J., Davoine, L., Dupont, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.18093108
Lambert, E., Saha, O., Landeira, B. S., de Farias, A. R. M., Hermant, X., Carrier, A., Pelletier, A., Gadaut, J., Davoine, L., Dupont, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.18093111
Terada, T., Therriault, J., Kang, M. S. P., Savard, M., Pascoal, T. A., Lussier, F. Z., Tissot, C., Wang, Y.-T., Benedet, A. L., Matsudaira, T., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14490235
Lambert, E., Saha, O., Landeira, B. S., de Farias, A. R. M., Hermant, X., Carrier, A., Pelletier, A., Gadaut, J., Davoine, L., Dupont, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.18093117
Lambert, E., Saha, O., Landeira, B. S., de Farias, A. R. M., Hermant, X., Carrier, A., Pelletier, A., Gadaut, J., Davoine, L., Dupont, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.18093105
Lambert, E., Saha, O., Landeira, B. S., de Farias, A. R. M., Hermant, X., Carrier, A., Pelletier, A., Gadaut, J., Davoine, L., Dupont, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.18093096
Biel, D., Brendel, M., Rubinski, A., Büerger, K., Janowitz, D., Dichgans, M., & Franzmeier, N. (2021) · Figshare · doi:10.6084/m9.figshare.15162146
Self-citationLi, L., Yu, X., Sheng, C., Jiang, X., Zhang, Q., Han, Y., & Jiang, J. (2022) · Figshare · doi:10.6084/m9.figshare.21130048
Lambert, E., Saha, O., Landeira, B. S., de Farias, A. R. M., Hermant, X., Carrier, A., Pelletier, A., Gadaut, J., Davoine, L., Dupont, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.18093093
Additional file 1 of Convergent lines of evidence support BIN1 as a risk gene of Alzheimer’s disease
Zhu, J., Liu, X., Yin, H., Gao, Y., & Yu, H. (2021) · Figshare · doi:10.6084/m9.figshare.13669536
Lambert, E., Saha, O., Landeira, B. S., de Farias, A. R. M., Hermant, X., Carrier, A., Pelletier, A., Gadaut, J., Davoine, L., Dupont, C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.18093099
- Authors
- Franzmeier, N., Rubinski, A., Neitzel, J., Ewers, M., (ADNI), T. A. D. N. I., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowski, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M. M., Potter, W., Snyder, P., Schwartz, A., Montine, T., Thomas, R. G., Donohue, M., Walter, S., Gessert, D., Sather, T., Jiminez, G., Harvey, D., Bernstein, M., Thompson, P., Schuff, N., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Cairns, N. J., Householder, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S. G., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Buckholtz, N., Albert, M., Frank, R., Hsiao, J., Kaye, J., Quinn, J., Lind, B., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Ances, B., Carroll, M., Leon, S., Mintun, M. A., Schneider, S., Oliver, A., Marson, D., Griffith, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Grossman, H., Mitsis, E., de Toledo-Morrell, L., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Roberts, P., Onyike, C., D’Agostino, D., Kielb, S., Galvin, J. E., Cerbone, B., Michel, C. A., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Doraiswamy, P. M., Petrella, J. R., Wong, T. Z., Arnold, S. E., Karlawish, J. H., Wolk, D., Smith, C. D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M. S., Brand, C., Mulnard, R. A., Thai, G., McAdams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Diaz-Arrastia, R., King, R., Weiner, M., Martin-Cook, K., DeVous, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Anderson, H. S., Swerdlow, R. H., Apostolova, L., Tingus, K., Woo, E., Silverman, D. H. S., Lu, P. H., Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Kendall, T., Johnson, H., Farlow, M. R., Hake, A. M., Matthews, B. R., Herring, S., Hunt, C., van Dyck, C. H., Carson, R. E., MacAvoy, M. G., Chertkow, H., Bergman, H., Hosein, C., Hsiung, G.-Y. R., Feldman, H., Mudge, B., Assaly, M., Bernick, C., Munic, D., Kertesz, A., Rogers, J., Trost, D., Kerwin, D., Lipowski, K., Wu, C.-K., Johnson, N., Sadowsky, C., Martinez, W., Villena, T., Turner, R. S., Johnson, K., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Frey, M., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M. N., Belden, C. M., Jacobson, S. A., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P. L., Allard, J., Lerner, A., Ogrocki, P., Hudson, L., Fletcher, E., Carmichael, O., Olichney, J., DeCarli, C., Kittur, S., Borrie, M., Lee, T.-Y., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Preda, A., Nguyen, D., Tariot, P., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Adeli, A., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Santulli, R. B., Kitzmiller, T. J., Schwartz, E. S., Sink, K. M., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rachinsky, I., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Schultz, S. K., Boles Ponto, L. L., Shim, H., Smith, K. E., Relkin, N., Chaing, G., Raudin, L., Smith, A., Fargher, K., Raj, B. A., Neylan, T., Grafman, J., Davis, M., Morrison, R., Hayes, J., Finley, S., Friedl, K., Fleischman, D., Arfanakis, K., James, O., Massoglia, D., Fruehling, J. J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., & Furst, A. J.
- Affiliations
- LMU Klinikum (DE)
- University of California, San Francisco (US)
- Mayo Clinic (US)
- University of Pennsylvania (US)
- University of Southern California (US)
- Brigham and Women's Hospital (US)
- Washington University in St. Louis (US)
- Siemens (Germany) (DE)
- University of Pittsburgh (US)
- Albert Einstein College of Medicine (US)
- Alzheimer's Drug Discovery Foundation (US)
- Northwestern University (US)
- Brown University (US)
- Eli Lilly (United States) (US)
- University of Washington (US)
- University of California, Los Angeles (US)
- University of Utah (US)
- Banner Alzheimer’s Institute (US)
- University of California, Irvine (US)
- Indiana University Bloomington (US)
- University of California San Diego (US)
- National Institutes of Health (US)
- Johns Hopkins University (US)
- Oregon Health & Science University (US)
- University of Michigan (US)
- Baylor College of Medicine (US)
- University of Alabama (US)
- Icahn School of Medicine at Mount Sinai (US)
- Rush University Medical Center (US)
- New York University (US)
- Duke Medical Center (US)
- University of Kentucky (US)
- University of Rochester Medicine (US)
- The University of Texas Southwestern Medical Center (US)
- Emory University (US)
- University of Kansas Medical Center (US)
- Mayo Clinic in Florida (US)
- Yale University (US)
- Jewish General Hospital (CA)
- University of British Columbia (CA)
- Cleveland Clinic (US)
- St Joseph's Health Care (CA)
- Palm Beach Neurology (US)
- Georgetown University Medical Center (US)
- Banner Sun Health Research Institute (US)
- Boston University (US)
- Howard University (US)
- Case Western Reserve University (US)
- University of California, Davis (US)
- University of Wisconsin–Madison (US)
- Dent Neurologic Institute (US)
- The Ohio State University (US)
- Albany Medical College (US)
- Hartford Hospital (US)
- Dartmouth–Hitchcock Medical Center (US)
- Wake Forest University Health Sciences (US)
- Rhode Island Hospital (US)
- Butler Hospital (US)
- Medical University of South Carolina (US)
- Nathan Kline Institute for Psychiatric Research (US)
- University of Iowa (US)
- Cornell University (US)
- University of South Florida (US)
- United States Department of Defense (US)
- Stanford University (US)
- Corresponding author
- Ewers, Michael
- ORCID
- Franzmeier, Nicolai
- Rubinski, Anna
- Neitzel, Julia
- Ewers, Michael
- Weiner, Michael W.
- Petersen, Ronald
- Jack, Clifford R.
- Jagust, William
- Trojanowski, John Q.
- Toga, Arthur W.
- Beckett, Laurel
- Green, Robert C.
- Saykin, Andrew J.
- Morris, John
- Shaw, Leslie M.
- Raichle, Marcus
- Paul, Steven
- Davies, Peter
- Fillit, Howard
- Hefti, Franz
- Holtzman, David
- Snyder, Peter
- Thomas, Ronald G.
- Donohue, Michael
- Walter, Sarah
- Thompson, Paul
- Vemuri, Prashanthi
- Jones, David
- Kantarci, Kejal
- Koeppe, Robert A.
- Reiman, Eric M.
- Chen, Kewei
- Lee, Virginia
- Korecka, Magdalena
- Crawford, Karen
- Foroud, Tatiana M.
- Potkin, Steven G.
- Shen, Li
- Faber, Kelley
- Kim, Sungeun
- Nho, Kwangsik
- Hsiao, John
- Kaye, Jeffrey
- Quinn, Joseph
- Schneider, Lon S.
- Fleisher, Adam
- Heidebrink, Judith L.
- Lord, Joanne L.
- Knopman, David
- Johnson, Kris
- Stern, Yaakov
- Honig, Lawrence S.
- Bell, Karen L.
- Ances, Beau
- Carroll, Maria
- Oliver, Angela
- Marson, Daniel
- Clark, David
- Geldmacher, David
- Roberson, Erik
- Shah, Raj C.
- Duara, Ranjan
- Onyike, Chiadi
- D’Agostino, Daniel
- Kielb, Stephanie
- Galvin, James E.
- Cerbone, Brittany
- Rusinek, Henry
- Glodzik, Lidia
- Doraiswamy, P Murali
- Petrella, Jeffrey R.
- Wong, Terence Z.
- Arnold, Steven E.
- Karlawish, Jason H.
- Wolk, David
- Smith, Charles D.
- Hardy, Peter
- Sinha, Partha
- Porsteinsson, Anton P.
- Ismail, M Saleem
- Thai, Gaby
- Womack, Kyle
- Quiceno, Mary
- Diaz-Arrastia, Ramon
- Weiner, Myron
- DeVous, Michael
- Levey, Allan I
- Lah, James J.
- Burns, Jeffrey M.
- Swerdlow, Russell H.
- Apostolova, Liana
- Silverman, Daniel H. S.
- Lu, Po H.
- Johnson, Heather
- Farlow, Martin R.
- Hake, Ann Marie
- Carson, Richard E.
- Chertkow, Howard
- Bergman, Howard
- Hsiung, Ging-Yuek Robin
- Feldman, Howard
- Bernick, Charles
- Kerwin, Diana
- Turner, Raymond Scott
- Sperling, Reisa A.
- Johnson, Keith A.
- Marshall, Gad
- Frey, Meghan
- Lane, Barton
- Rosen, Allyson
- Sabbagh, Marwan N.
- Belden, Christine M.
- Jacobson, Sandra A.
- Kowall, Neil
- Killiany, Ronald
- Budson, Andrew E.
- Norbash, Alexander
- Lerner, Alan
- Fletcher, Evan
- Carmichael, Owen
- Olichney, John
- DeCarli, Charles
- Johnson, Sterling
- Asthana, Sanjay
- Carlsson, Cynthia M.
- Preda, Adrian
- Nguyen, Dana
- Tariot, Pierre
- Scharre, Douglas W.
- Kataki, Maria
- Pearlson, Godfrey D.
- Santulli, Robert B.
- Sink, Kaycee M.
- Williamson, Jeff D.
- Garg, Pradeep
- Ott, Brian R.
- Tremont, Geoffrey
- Salloway, Stephen
- Correia, Stephen
- Miller, Bruce L.
- Mintzer, Jacobo
- Bachman, David
- Pasternak, Stephen
- Pomara, Nunzio
- Schultz, Susan K.
- Shim, Hyungsub
- Relkin, Norman
- Smith, Amanda
- Neylan, Thomas
- Grafman, Jordan
- Hayes, Jacqueline
- Friedl, Karl
- Fleischman, Debra
- Arfanakis, Konstantinos
- Peskind, Elaine R.
- Petrie, Eric C.
- Yesavage, Jerome A.
- Taylor, Joy L.
- Furst, Ansgar J.
- Venue
- Nature Communications
- Published
- 2019-04-16
- Volume
- 10
- Issue
- 1
- Pages
- 1766-1766
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6467911
- OpenAlex
- W2939459090
- Cited by
- 109
- References
- 74
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 13 · 2023: 9 · 2022: 25 · 2021: 23 · 2020: 13 · 2019: 4
- FWCI
- 11.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by)
- Scholarship@Western (Western University) (submittedVersion)
- Funders
- U.S. Department of Defense (U01 AG024904, W81XWH, W81XWH-12-2-, W81XWH-12, W81XWH1220012, AG024904)
- Foundation for the National Institutes of Health (W81XWH-12-2-0012, U01AG024904, Grant U01 AG024904, AG024904)
- Alzheimer's Association (U01 AG024904, W81XWH-12-2-0012)
- Bristol-Myers Squibb (U01 AG024904, AG024904, W81XWH-12-2-0012)
- Eli Lilly and Company (U01 AG024904, AG024904, W81XWH-12-2-0012)
- Pfizer (AG024904, W81XWH-12-2-0012, U01 AG024904)
- Biogen (W81XWH-12-2-0012, U01 AG024904, AG024904)
- F. Hoffmann-La Roche (W81XWH-12-2-0012, AG024904, U01 AG024904)
- Meso Scale Diagnostics (U01 AG024904, AG024904, W81XWH-12-2-0012)
- Alzheimer's Disease Neuroimaging Initiative (W81XWH-12-2–0012, U01AG024904, AG024904, W81XWH-12-2-, Department of Defense award number W81XWH-12-2-0012)
- BioClinica (U01 AG024904, W81XWH-12-2-0012, AG024904)
- Novartis Pharmaceuticals Corporation (W81XWH-12-2-0012, U01 AG024904, AG024904)
- Alzheimer Forschung Initiative (15035)
- European Commission (U01 AG024904, 334259, W81XWH-12-2-0012)
- Eisai (W81XWH-12-2-0012, U01 AG024904, AG024904)
- Servier (AG024904, W81XWH-12-2-0012, U01 AG024904)
- H. Lundbeck A/S (U01 AG024904, AG024904, W81XWH-12-2-0012)
- IXICO (AG024904, W81XWH-12-2-0012, U01 AG024904)
- National Institutes of Health (3u01ag024904-10s2, W81XWH, W81XWH-12-2-0012, U01-AG024904, Grant U01 AG024904, AG024904, UL1TR002369)
- Genentech (W81XWH-12-2-0012, AG024904, U01 AG024904)
- Canadian Institutes of Health Research (U01 AG024904, W81XWH-12-2-0012)
- National Institute on Aging (U01-AG-024904, P30AG010129, W81XWH-12-2–0012, AG 024904, P30AG008017, R01AG054076)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- BIN1, Alzheimer's disease risk, tau pathology, tau PET, memory impairment, Braak stages, genetic risk factors, older adults without dementia, amyloid-beta
- MeSH terms
- Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Brain, Cognition, Cytoskeleton, Endocytosis, Female, Humans, Magnetic Resonance Imaging, Male, Memory, Nuclear Proteins, Risk Factors, Genetic Variation, tau Proteins, Polymorphism, Single Nucleotide, Tumor Suppressor Proteins, Adaptor Proteins, Signal Transducing, Positron-Emission Tomography
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.
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