CoChat
Sign Up
Cited by 57Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

KL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer’s disease

Open access
Neitzel, Julia, Franzmeier, Nicolai, Rubinski, Anna, Dichgans, Martin, Brendel, Matthias, Alzheimer’s Disease Neuroimaging Initiative (ADNI), Weiner, Michael, Aisen, Paul +285 more·2021·Nature Communications
DOI 10.1038/s41467-021-23755-zPMC PMC8219708
Open this paper in CoChat — free accountOpen PDF

Abstract

Klotho-VS heterozygosity (KL-VS het) is associated with reduced risk of Alzheimer’s disease (AD). However, whether KL-VS het is associated with lower levels of pathologic tau, i.e., the key AD pathology driving neurodegeneration and cognitive decline, is unknown. Here, we assessed the interaction between KL-VS het and levels of beta-amyloid, a key driver of tau pathology, on the levels of PET-assessed neurofibrillary tau in 551 controls and patients across the AD continuum. KL-VS het showed lower cross-sectional and longitudinal increase in tau-PET per unit increase in amyloid-PET when compared to that of non-carriers. This association of KL-VS het on tau-PET was stronger in Klotho mRNA-expressing brain regions mapped onto a gene expression atlas. KL-VS het was related to better memory functions in amyloid-positive participants and this association was mediated by lower tau-PET. Amyloid-PET levels did not differ between KL-VS het carriers versus non-carriers. Together, our findings provide evidence to suggest a protective role of KL-VS het against amyloid-related tau pathology and tau-related memory impairments in elderly humans at risk of AD dementia.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41467-021-23755-z

Cites

7 of 7 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • KLOTHO-VS heterozygosity has been reported to decrease Aβ plaque deposition, tau accumulation and tau-mediated cognitive impairment.

    “Of particular interest is the longevity-increasing KLOTHO-VS heterozygosity, which has been reported to operate by decreasing Aβ plaque deposition, tau accumulation and tau-mediated cognitive impairment23–26.”

    From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [25]

    The Results report lower amyloid-related tau accumulation in KL-VS heterozygotes, and the Abstract reports better memory in amyloid-positive carriers mediated by lower tau-PET. But the Abstract says amyloid-PET levels did not differ between carriers and non-carriers; the Results find lower amyloid-PET only in a restricted subgroup of a larger sample. The paper reports associations, not an established mechanism by which heterozygosity decreases all three outcomes. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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

Flagged first, then by citations

Research works printed but not linked: 56

  1. [1]Kuro-o M Mutation of the mouse klotho gene leads to a syndrome resembling ageing Nature 1997 390 45 51 10.1038/36285 9363890 · DOI · Paper page
  2. [2]Zhu Z Klotho gene polymorphisms are associated with healthy aging and longevity: Evidence from a meta-analysis Mech. Ageing Dev. 2019 178 33 40 10.1016/j.mad.2018.12.003 30633899 · DOI
  3. [3]Kuro-o M The Klotho proteins in health and disease Nat. Rev. Nephrol. 2019 15 27 44 10.1038/s41581-018-0078-3 30455427 · DOI · Paper page
  4. [4]Kurosu H Suppression of aging in mice by the hormone Klotho Science 2005 309 1829 1833 10.1126/science.1112766 16123266 PMC2536606 · DOI · Paper page
  5. [5]Dubal DB Life extension factor klotho enhances cognition Cell Rep. 2014 7 1065 1076 10.1016/j.celrep.2014.03.076 24813892 PMC4176932 · DOI
  6. [6]Arking DE Atzmon G Arking A Barzilai N Dietz HC Association between a functional variant of the KLOTHO gene and high-density lipoprotein cholesterol, blood pressure, stroke, and longevity Circ. Res. 2005 96 412 418 10.1161/01.RES.0000157171.04054.30 15677572 · DOI
  7. [7]Mengel-From J Genetic variants in KLOTHO associate with cognitive function in the oldest old group J. Gerontol. A Biol. Sci. Med Sci. 2016 71 1151 1159 10.1093/gerona/glv163 26405063 PMC4978356 · DOI
  8. [8]Yokoyama JS Variation in longevity gene KLOTHO is associated with greater cortical volumes Ann. Clin. Transl. Neurol. 2015 2 215 230 10.1002/acn3.161 25815349 PMC4369272 · DOI
  9. [9]Deary IJ KLOTHO genotype and cognitive ability in childhood and old age in the same individuals Neurosc Lett. 2005 378 22 27 10.1016/j.neulet.2004.12.005 15763166 · DOI
  10. [10]de Vries CF Klotho, APOEε4, cognitive ability, brain size, atrophy, and survival: a study in the Aberdeen Birth Cohort of 1936 Neurobiol. Aging 2017 55 91 98 10.1016/j.neurobiolaging.2017.02.019 28431289 · DOI
  11. [11]Zeng C-Y Lentiviral vector–mediated overexpression of Klotho in the brain improves Alzheimer’s disease–like pathology and cognitive deficits in mice Neurobiol. Aging 2019 78 18 28 10.1016/j.neurobiolaging.2019.02.003 30851437 · DOI
  12. [12]Barker WW Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank Alzheimer Dis. Assoc. Disord. 2002 16 203 212 10.1097/00002093-200210000-00001 12468894 · DOI
  13. [13]Belloy ME Association of Klotho-VS heterozygosity with risk of Alzheimer disease in individuals who carry APOE4 JAMA Neurol. 2020 7 849 862 10.1001/jamaneurol.2020.0414 PMC7154955 32282020 · DOI · Paper page
  14. [14]Jansen WJ Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis JAMA 2015 313 1924 1938 10.1001/jama.2015.4668 25988462 PMC4486209 · DOI · Paper page
  15. [15]Corder EH Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families Science 1993 261 921 923 10.1126/science.8346443 8346443 · DOI · Paper page
  16. [16]Erickson CM KLOTHO heterozygosity attenuates APOE4-related amyloid burden in preclinical AD Neurology 2019 92 e1878 e1889 10.1212/WNL.0000000000007323 30867273 PMC6550504 · DOI · Paper page
  17. [17]Bejanin A Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer’s disease Brain 2017 140 3286 3300 10.1093/brain/awx243 29053874 PMC5841139 · DOI · Paper page
  18. [18]Bateman RJ Clinical and biomarker changes in dominantly inherited Alzheimer’s disease N. Engl. J. Med. 2012 367 795 804 10.1056/NEJMoa1202753 22784036 PMC3474597 · DOI · Paper page
  19. [21]Guo, T. et al. Longitudinal cognitive and biomarker measurements support a unidirectional pathway in Alzheimer’s Disease pathophysiology. Biol. Psychiatry89, 786–794 (2021). PMC9682985 32919611
  20. [22]Jack CR Jr Predicting future rates of tau accumulation on PET Brain 2020 143 3136 3150 10.1093/brain/awaa248 33094327 PMC7586089 · DOI · Paper page
  21. [23]Harrison TM Longitudinal tau accumulation and atrophy in aging and alzheimer disease Ann. Neurol. 2019 85 229 240 10.1002/ana.25406 30597624 PMC6579738 · DOI
  22. [24]LaPoint MR The association between tau PET and retrospective cortical thinning in clinically normal elderly Neuroimage 2017 157 612 622 10.1016/j.neuroimage.2017.05.049 28545932 PMC5772972 · DOI
  23. [25]Hanseeuw BJ Fluorodeoxyglucose metabolism associated with tau‐amyloid interaction predicts memory decline Ann. Neurol. 2017 81 583 596 10.1002/ana.24910 28253546 PMC5404378 · DOI · Paper page
  24. [26]Johnson KA Tau positron emission tomographic imaging in aging and early Alzheimer disease Ann. Neurol. 2016 79 110 119 10.1002/ana.24546 26505746 PMC4738026 · DOI · Paper page
  25. [27]Ossenkoppele R Associations between tau, Aβ, and cortical thickness with cognition in Alzheimer disease Neurology 2019 92 e601 e612 10.1212/WNL.0000000000006875 30626656 PMC6382060 · DOI
  26. [29]La Joie R Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET Sci. Transl. Med. 2020 12 eaau5732 10.1126/scitranslmed.aau5732 31894103 PMC7035952 · DOI · Paper page
  27. [30]Kuang X Klotho upregulation contributes to the neuroprotection of ligustilide in an Alzheimer’s disease mouse model Neurobiol. Aging 2014 35 169 178 10.1016/j.neurobiolaging.2013.07.019 23973442 · DOI
  28. [31]Dubal DB Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice J. Neurosci. 2015 35 2358 2371 10.1523/JNEUROSCI.5791-12.2015 25673831 PMC4323521 · DOI
  29. [32]Weiner MW The Alzheimer’s Disease Neuroimaging Initiative 3: continued innovation for clinical trial improvement Alzheimers Dement. 2017 13 561 571 10.1016/j.jalz.2016.10.006 27931796 PMC5536850 · DOI
  30. [33]Hawrylycz MJ An anatomically comprehensive atlas of the adult human brain transcriptome Nature 2012 489 391 399 10.1038/nature11405 22996553 PMC4243026 · DOI · Paper page
  31. [35]Pontecorvo MJ Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition Brain 2017 140 748 763 28077397 PMC5382945
  32. [36]Lockhart SN Amyloid and tau PET demonstrate region-specific associations in normal older people Neuroimage 2017 150 191 199 10.1016/j.neuroimage.2017.02.051 28232190 PMC5391247 · DOI
  33. [37]Sepulcre J In vivo tau, amyloid, and gray matter profiles in the aging brain J. Neurosci. 2016 36 7364 7374 10.1523/JNEUROSCI.0639-16.2016 27413148 PMC4945661 · DOI
  34. [38]French L Paus T A FreeSurfer view of the cortical transcriptome generated from the Allen Human Brain Atlas Front Neurosci. 2015 9 323 10.3389/fnins.2015.00323 26441498 PMC4584957 · DOI
  35. [39]Crane PK Development and assessment of a composite score for memory in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) Brain Imaging Behav. 2012 6 502 516 10.1007/s11682-012-9186-z 22782295 PMC3806057 · DOI
  36. [40]Dumitrescu L Genetic variants and functional pathways associated with resilience to Alzheimer’s disease Brain 2020 143 2561 2575 10.1093/brain/awaa209 32844198 PMC7447518 · DOI
  37. [41]Franzmeier, N. et al. The BDNF Val66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer’s disease. Mol. Psychiatry26, 614–628 (2021). PMC6754794 30899092
  38. [42]Hohman TJ Dumitrescu L Cox NJ Jefferson AL Genetic resilience to amyloid related cognitive decline Brain Imaging Behav. 2017 11 401 409 10.1007/s11682-016-9615-5 27743375 PMC5392179 · DOI
  39. [43]Kleineidam L PLCG2 protective variant p. P522R modulates Tau pathology and disease progression in patients with mild cognitive impairment Acta Neuropathol. 2020 139 1025 1044 10.1007/s00401-020-02138-6 32166339 PMC7244617 · DOI · Paper page
  40. [44]Porter T Klotho allele status is not associated with Abeta and APOE epsilon4-related cognitive decline in preclinical Alzheimer’s disease Neurobiol. Aging 2019 76 162 165 10.1016/j.neurobiolaging.2018.12.014 30716541 · DOI
  41. [45]Urakawa I Klotho converts canonical FGF receptor into a specific receptor for FGF23 Nature 2006 444 770 774 10.1038/nature05315 17086194 · DOI
  42. [46]Zeldich E The neuroprotective effect of Klotho is mediated via regulation of members of the redox system J. Biol. Chem. 2014 289 24700 24715 10.1074/jbc.M114.567321 25037225 PMC4148892 · DOI
  43. [47]Chang Q The b-glucuronidase Klotho hydrolyzes and activates the TRPV5 channel Science 2005 310 490 493 10.1126/science.1114245 16239475 · DOI
  44. [48]Fernandez AF Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice Nature 2018 558 136 140 10.1038/s41586-018-0162-7 29849149 PMC5992097 · DOI · Paper page
  45. [49]Uddin MS Autophagy and Alzheimer’s disease: from molecular mechanisms to therapeutic implications Front Aging Neurosci. 2018 10 4 10.3389/fnagi.2018.00004 PMC5797541 29441009 · DOI
  46. [50]Kuang X Neuroprotective effect of ligustilide through induction of α-secretase processing of both APP and Klotho in a mouse model of Alzheimer’s disease Front Aging Neurosci. 2017 9 353 10.3389/fnagi.2017.00353 29163135 PMC5673635 · DOI
  47. [52]Semba RD Klotho in the cerebrospinal fluid of adults with and without Alzheimer’s disease Neurosci. Lett. 2014 558 37 40 10.1016/j.neulet.2013.10.058 24211693 PMC4037850 · DOI
  48. [53]Rhee E Relationship between polymorphisms G395A in promoter and C1818T in exon 4 of the KLOTHO gene with glucose metabolism and cardiovascular risk factors in Korean women J. Endocrinol. Invest 2006 29 613 618 10.1007/BF03344160 16957409 · DOI
  49. [54]Yamazaki Y Establishment of sandwich ELISA for soluble alpha-Klotho measurement: age-dependent change of soluble alpha-Klotho levels in healthy subjects Biochem Biophys. Res Commun. 2010 398 513 518 10.1016/j.bbrc.2010.06.110 20599764 PMC4130489 · DOI
  50. [55]Yokoyama JS Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging Brain Imaging Behav. 2017 11 391 400 10.1007/s11682-016-9598-2 27714549 PMC5382127 · DOI
  51. [56]Cole MA Seabrook GR On the horizon—the value and promise of the global pipeline of Alzheimer’s disease therapeutics Alzheimers Dement 2020 6 e12009 PMC7217086 32405530
  52. [57]Desikan RS An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest Neuroimage 2006 31 968 980 10.1016/j.neuroimage.2006.01.021 16530430 · DOI · Paper page
  53. [58]Landau SM Amyloid deposition, hypometabolism, and longitudinal cognitive decline Ann. Neurol. 2012 72 578 586 10.1002/ana.23650 23109153 PMC3786871 · DOI
  54. [59]Maass A Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer’s disease Neuroimage 2017 157 448 463 10.1016/j.neuroimage.2017.05.058 28587897 PMC5814575 · DOI · Paper page
  55. [60]Marquié M Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue Ann. Neurol. 2015 78 787 800 10.1002/ana.24517 26344059 PMC4900162 · DOI · Paper page
  56. [61]Grothe MJ Molecular properties underlying regional vulnerability to Alzheimer’s disease pathology Brain 2018 141 2755 2771 30016411 PMC6113636

Cited by

Sorted by citations

Authors
Neitzel, J., Franzmeier, N., Rubinski, A., Dichgans, M., Brendel, M., (ADNI), A. D. N. I., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Liu, E., Montine, T., Thomas, R. G., Donohue, M., Walter, S., Gessert, D., Sather, T., Jiminez, G., Harvey, D., Bernstein, M., Fox, N., Thompson, P., Schuff, N., DeCArli, C., 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., Reinwald, L. T., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Kelley, F., Kim, S., Nho, K., Kachaturian, Z., Frank, R., Snyder, P. J., Molchan, S., 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., Meyer, J. V., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Ances, B., Morris, J. C., Carroll, M., Leon, S., Mintun, M. A., Schneider, S., OliverNG, A., Griffith, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Grossman, H., Mitsis, E., deToledo-Morrell, L., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Roberts, P., Albert, M., Onyike, C., D’Agostino, D., Kielb, S., Galvin, J. E., Pogorelec, D. M., 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., Mc Adams Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Arrastia, R. D., King, R., Weiner, M., Cook, K. M., 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., Radford, N. R. G., ParfittH, 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., Black, S., Stefanovic, B., Caldwell, C., Hsiung, G. Y. R., Feldman, H., Mudge, B., Past, M. A., Kertesz, A., Rogers, J., Trost, D., Bernick, C., Munic, D., Kerwin, D., Mesulam, M. M., 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., Yesavage, J., Taylor, J. L., 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., Obisesan, T. O., Wolday, S., 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., Potkin, S. G., 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., SinkS, 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., Finger, E., Pasternak, S., Rachinsky, I., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Schultz, S. K., Ponto, L. L. B., Shim, H., Smith, K. E., Relkin, N., Chaing, G., Raudin, L., Smith, A., Fargher, K., Raj, B. A., Malik, R., & Ewers, M.
Affiliations
  • Erasmus MC (NL)
  • Institut für Schlaganfall- und Demenzforschung (DE)
  • German Center for Neurodegenerative Diseases (DE)
  • 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)
  • Janssen Alzheimer Immunotherapy Research & Development (United States) (US)
  • University of Washington (US)
  • University of California San Diego (US)
  • University of Utah (US)
  • Banner Alzheimer’s Institute (US)
  • University of Pittsburgh (US)
  • University of California, Irvine (US)
  • Indiana University Bloomington (US)
  • Alzheimer's Association (US)
  • General Electric (United States) (US)
  • National Institutes of Health (US)
  • Oregon Health & Science University (US)
  • University of Michigan (US)
  • Baylor College of Medicine (US)
  • Columbia University Irving Medical Center (US)
  • University of Alabama at Birmingham (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • Rush University Medical Center (US)
  • Johns Hopkins University (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)
  • University of California, Los Angeles (US)
  • Mayo Clinic in Florida (US)
  • Yale University (US)
  • Jewish General Hospital (CA)
  • Sunnybrook Health Science Centre (CA)
  • University of British Columbia (CA)
  • St Joseph's Health Centre (CA)
  • Cleveland Clinic (US)
  • Northwestern University (US)
  • Palm Beach Neurology (US)
  • Georgetown University Medical Center (US)
  • Stanford University (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)
Corresponding author
  • Neitzel, Julia
  • Ewers, Michael
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-06-22
Volume
12
Issue
1
Pages
3825-3825
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-021-23755-z
PMC
PMC8219708
OpenAlex
W3174077948
Cited by
57
References
7
Citations by year
2026: 2 · 2025: 12 · 2024: 15 · 2023: 11 · 2022: 15 · 2021: 2
FWCI
6.75
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
  • Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by)
  • eScholarship (California Digital Library) (submittedVersion, other-oa)
  • Civil War Book Review (submittedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • Scholarship@Western (Western University) (submittedVersion)
  • DZNE Pub (submittedVersion, other-oa)
  • IUScholarWorks (Indiana University) (submittedVersion, cc-by)
Funders
Alzheimer Forschung Initiative (15035)
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
Alzheimer's disease, tau accumulation, amyloid-beta, memory impairment, amyloid PET, tau PET, genetic risk, neurodegeneration, gene expression atlas, protective genetic variants
MeSH terms
Klotho Proteins, Aged, Alzheimer Disease, Apolipoproteins E, Brain, Female, Glucuronidase, Heterozygote, Humans, Male, Memory Disorders, Middle Aged, Protein Binding, Gene Expression, Amyloid beta-Peptides, tau Proteins, Polymorphism, Single Nucleotide, 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 ›

Are you an author, or do you see a problem with this page? Request a review