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Cited by 109Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory

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Franzmeier, Nicolai, Rubinski, Anna, Neitzel, Julia, Ewers, Michael, The Alzheimer’s Disease Neuroimaging Initiative (ADNI), Weiner, Michael W., Aisen, Paul, 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., Khachaturian, Zaven, Sorensen, Greg, Kuller, Lew, Raichle, Marcus, Paul, Steven, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, David, Mesulam, Marek M., Potter, William, Snyder, Peter, Schwartz, Adam, Montine, Tom, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jiminez, Gus, Harvey, Danielle, Bernstein, Matthew, Thompson, Paul, Schuff, Norbert, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Mathis, Chet, Landau, Susan, Cairns, Nigel J., Householder, Erin, Taylor-Reinwald, Lisa, Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Crawford, Karen, Neu, Scott, Foroud, Tatiana M., Potkin, Steven G., Shen, Li, Faber, Kelley, Kim, Sungeun, Nho, Kwangsik, Thal, Leon, Buckholtz, Neil, Albert, Marylyn, Frank, Richard, Hsiao, John, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Carter, Raina, Dolen, Sara, Schneider, Lon S., Pawluczyk, Sonia, Beccera, Mauricio, Teodoro, Liberty, Spann, Bryan M., Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L., Lord, Joanne L., Mason, Sara S., Albers, Colleen S., Knopman, David, Johnson, Kris, Doody, Rachelle S., Villanueva-Meyer, Javier, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A., Schneider, Stacy, Oliver, Angela, Marson, Daniel, Griffith, Randall, Clark, David, Geldmacher, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, de Toledo-Morrell, Leyla, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Greig, Maria T., Roberts, Peggy, Onyike, Chiadi, D’Agostino, Daniel, Kielb, Stephanie, Galvin, James E., Cerbone, Brittany, Michel, Christina A., Rusinek, Henry, de Leon, Mony J., Glodzik, Lidia, De Santi, Susan, Doraiswamy, P Murali, Petrella, Jeffrey R., Wong, Terence Z., Arnold, Steven E., Karlawish, Jason H., Wolk, David, Smith, Charles D., Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Porsteinsson, Anton P., Goldstein, Bonnie S., Martin, Kim, Makino, Kelly M., Ismail, M Saleem, Brand, Connie, Mulnard, Ruth A., Thai, Gaby, McAdams-Ortiz, Catherine, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I, Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Swerdlow, Russell H., Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H. S., Lu, Po H., Bartzokis, George, Graff-Radford, Neill R., Parfitt, Francine, Kendall, Tracy, Johnson, Heather, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Herring, Scott, Hunt, Cynthia, van Dyck, Christopher H., Carson, Richard E., MacAvoy, Martha G., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Hsiung, Ging-Yuek Robin, Feldman, Howard, Mudge, Benita, Assaly, Michele, Bernick, Charles, Munic, Donna, Kertesz, Andrew, Rogers, John, Trost, Dick, Kerwin, Diana, Lipowski, Kristine, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad, Frey, Meghan, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N., Belden, Christine M., Jacobson, Sandra A., Sirrel, Sherye A., Kowall, Neil, Killiany, Ronald, Budson, Andrew E., Norbash, Alexander, Johnson, Patricia Lynn, Allard, Joanne, Lerner, Alan, Ogrocki, Paula, Hudson, Leon, Fletcher, Evan, Carmichael, Owen, Olichney, John, DeCarli, Charles, Kittur, Smita, Borrie, Michael, Lee, T-Y., Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W., Kataki, Maria, Adeli, Anahita, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Santulli, Robert B., Kitzmiller, Tamar J., Schwartz, Eben S., Sink, Kaycee M., Williamson, Jeff D., Garg, Pradeep, Watkins, Franklin, Ott, Brian R., Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Pasternak, Stephen, Rachinsky, Irina, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K., Boles Ponto, Laura L., Shim, Hyungsub, Smith, Karen Elizabeth, Relkin, Norman, Chaing, Gloria, Raudin, Lisa, Smith, Amanda, Fargher, Kristin, Raj, Balebail Ashok, Neylan, Thomas, Grafman, Jordan, Davis, Melissa, Morrison, Rosemary, Hayes, Jacqueline, Finley, Shannon, Friedl, Karl, Fleischman, Debra, Arfanakis, Konstantinos, James, Olga, Massoglia, Dino, Fruehling, J Jay, Harding, Sandra, Peskind, Elaine R., Petrie, Eric C., Li, Gail, Yesavage, Jerome A., Taylor, Joy L., Furst, Ansgar J.·2019·Nature Communications
DOI 10.1038/s41467-019-09564-5PMC PMC6467911
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Abstract

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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Figures

Fig. 1 Staging systems for tau- and amyloid-PET. Spatial mapping of Braak- (a) and amyloid stage-specific ROIs (b) that were used to determine regional AV1451 tau- and AV45 amyloid-PET uptake within the sample of n = 89 subjects
Fig. 1 Staging systems for tau- and amyloid-PET. Spatial mapping of Braak- (a) and amyloid stage-specific ROIs (b) that were used to determine regional AV1451 tau- and AV45 amyloid-PET uptake within the sample of n = 89 subjectsCC BY · PubMed Central
Fig. 2 Effects of BIN1 rs744373 on tau- and amyloid-PET uptake. a Boxplots showing the differences in global or regional AV1451 tau-PET SUVRs between BIN1 rs744373 risk allele (n = 40, yellow) vs. normal-allele carriers (n = 49, blue). P-values are based on ANCOVA models controlled for age, gender, education, diagnosis, memory performance (i.e., ADNI-MEM) and gray matter volume of the respective ROI. b Differences in global or regional AV45 amyloid-PET uptake between BIN1 rs744373 risk allele (n = 40, yellow) vs. normal-allele carriers (n = 49, blue). Boxplots are displayed as median (center line) ±interquartile range (box boundaries) with whiskers including observations falling within the 1.5 interquartile range. P-values are again derived from ANCOVA models controlled for age, gender, education, diagnosis, ApoE ε4 carrier status, and gray matter volume of the respective ROI. *p < 0.05 (uncorrected); ‘ = significant after Bonferroni correction (p < 0.0071)
Fig. 2 Effects of BIN1 rs744373 on tau- and amyloid-PET uptake. a Boxplots showing the differences in global or regional AV1451 tau-PET SUVRs between BIN1 rs744373 risk allele (n = 40, yellow) vs. normal-allele carriers (n = 49, blue). P-values are based on ANCOVA models controlled for age, gender, education, diagnosis, memory performance (i.e., ADNI-MEM) and gray matter volume of the respective ROI. b Differences in global or regional AV45 amyloid-PET uptake between BIN1 rs744373 risk allele (n = 40, yellow) vs. normal-allele carriers (n = 49, blue). Boxplots are displayed as median (center line) ±interquartile range (box boundaries) with whiskers including observations falling within the 1.5 interquartile range. P-values are again derived from ANCOVA models controlled for age, gender, education, diagnosis, ApoE ε4 carrier status, and gray matter volume of the respective ROI. *p < 0.05 (uncorrected); ‘ = significant after Bonferroni correction (p < 0.0071)CC BY · PubMed Central
Fig. 3 BIN1 rs744373 effects on tau across the amyloid spectrum. Boxplot showing the association between BIN1 rs744373 (risk-allele n = 40, yellow; normal-allele n = 49, blue) and global AV1451 tau-PET uptake across amyloid quartiles. The statistical main effects presented in the upper left corner of the graph are derived from linear regression, with the BIN1 rs7443733 SNP and global AV45 amyloid-PET SUVR as predictors, controlling for age, gender, diagnosis, and ApoE ε4 status. Cohens d effects sizes displayed in the plot were derived for each quartile. Note, that no interaction between BIN1 rs744373 and global AV45 amyloid-PET uptake was found, suggesting that the effects of BIN1 rs744373 on tau are similar between high- and low-amyloid groups. Boxplots are displayed as median (center line) ±interquartile range (box boundaries) with whiskers including observations falling within the 1.5 interquartile range
Fig. 3 BIN1 rs744373 effects on tau across the amyloid spectrum. Boxplot showing the association between BIN1 rs744373 (risk-allele n = 40, yellow; normal-allele n = 49, blue) and global AV1451 tau-PET uptake across amyloid quartiles. The statistical main effects presented in the upper left corner of the graph are derived from linear regression, with the BIN1 rs7443733 SNP and global AV45 amyloid-PET SUVR as predictors, controlling for age, gender, diagnosis, and ApoE ε4 status. Cohens d effects sizes displayed in the plot were derived for each quartile. Note, that no interaction between BIN1 rs744373 and global AV45 amyloid-PET uptake was found, suggesting that the effects of BIN1 rs744373 on tau are similar between high- and low-amyloid groups. Boxplots are displayed as median (center line) ±interquartile range (box boundaries) with whiskers including observations falling within the 1.5 interquartile rangeCC BY · PubMed Central
Fig. 4 Spatial patterns of tau-PET and BIN1 mRNA expression. Spatial mapping of median BIN1 mRNA expression (i.e., log2) derived from the Allen Brain Atlas and group-median AV1451 tau-PET SUVR (derived from n = 89 subjects), either for all ROIs (upper panel) or restricted to regions falling above the 75th percentile of either BIN1 mRNA expression or group-median AV1451 tau-PET uptake (lower panel). Color scales represent SUVR scores for AV1451 tau-PET and log2 mRNA expression for BIN1 mRNA
Fig. 4 Spatial patterns of tau-PET and BIN1 mRNA expression. Spatial mapping of median BIN1 mRNA expression (i.e., log2) derived from the Allen Brain Atlas and group-median AV1451 tau-PET SUVR (derived from n = 89 subjects), either for all ROIs (upper panel) or restricted to regions falling above the 75th percentile of either BIN1 mRNA expression or group-median AV1451 tau-PET uptake (lower panel). Color scales represent SUVR scores for AV1451 tau-PET and log2 mRNA expression for BIN1 mRNACC BY · PubMed Central
Fig. 5 Association between tau-PET and BIN1 mRNA expression. Scatterplot showing the positive association between ROI-based BIN1 mRNA expression obtained from the Allen Brain Atlas and group-median AV1451 tau-PET uptake (Number of ROIs = 34; Association illustrated as least-squares regression line ±95% confidence interval). P-values and 95% confidence intervals of r-values are derived from bootstrapped spatial regression with 1000 iterations
Fig. 5 Association between tau-PET and BIN1 mRNA expression. Scatterplot showing the positive association between ROI-based BIN1 mRNA expression obtained from the Allen Brain Atlas and group-median AV1451 tau-PET uptake (Number of ROIs = 34; Association illustrated as least-squares regression line ±95% confidence interval). P-values and 95% confidence intervals of r-values are derived from bootstrapped spatial regression with 1000 iterationsCC BY · PubMed Central
Fig. 6 Tau mediates effects of BIN1 rs744373 on memory impairment. Path diagram of the mediation model (assessed on the full sample of n = 89 subjects), showing that associations between BIN1 rs744373 risk-allele carriage and worse memory are mediated via global AV1451 tau-PET uptake. Path-weights are displayed as beta values with standard errors in brackets. All paths are controlled for age, gender, education, diagnosis, global AV45 amyloid-PET uptake, and ApoE ε4 carrier status. Asterisks indicate p-values below 0.05. Significance of the indirect effect was determined using bootstrapping with 10,000 iterations
Fig. 6 Tau mediates effects of BIN1 rs744373 on memory impairment. Path diagram of the mediation model (assessed on the full sample of n = 89 subjects), showing that associations between BIN1 rs744373 risk-allele carriage and worse memory are mediated via global AV1451 tau-PET uptake. Path-weights are displayed as beta values with standard errors in brackets. All paths are controlled for age, gender, education, diagnosis, global AV45 amyloid-PET uptake, and ApoE ε4 carrier status. Asterisks indicate p-values below 0.05. Significance of the indirect effect was determined using bootstrapping with 10,000 iterationsCC BY · PubMed Central

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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)
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  • Rhode Island Hospital (US)
  • Butler Hospital (US)
  • Medical University of South Carolina (US)
  • Nathan Kline Institute for Psychiatric Research (US)
  • University of Iowa (US)
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  • United States Department of Defense (US)
  • Stanford University (US)
Corresponding author
Ewers, Michael
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-04-16
Volume
10
Issue
1
Pages
1766-1766
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-09564-5
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
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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
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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.

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 ›

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