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

被引：61

作者：

Franzmeier, Nicolai ^{[1
,2
]}

Rubinski, Anna ^{[1
,2
]}

Neitzel, Julia ^{[1
]}

Ewers, Michael ^{[1
,2
]}

Weiner, Michael W. ^{[3
]}

Aisen, Paul ^{[4
]}

Weiner, Michael ^{[3
]}

Aisen, Paul ^{[4
]}

Petersen, Ronald ^{[5
]}

Jack, Clifford R., Jr. ^{[5
]}

Jagust, William ^{[6
]}

Trojanowki, John Q. ^{[7
,31
]}

Toga, Arthur W. ^{[4
,8
]}

Beckett, Laurel ^{[9
]}

Green, Robert C. ^{[10
]}

Saykin, Andrew J. ^{[11
]}

Morris, John ^{[12
]}

Shaw, Leslie M. ^{[7
,31
]}

Khachaturian, Zaven ^{[13
]}

Sorensen, Greg ^{[14
]}

Carrillo, Maria

Kuller, Lew ^{[15
]}

Raichle, Marc ^{[12
]}

Paul, Steven ^{[16
]}

Davies, Peter ^{[17
]}

Fillit, Howard ^{[18
]}

Hefti, Franz ^{[19
]}

Holtzman, David ^{[12
]}

Mesulam, M. Marcel ^{[20
]}

Potter, William ^{[21
]}

Snyder, Peter ^{[22
]}

Logovinsky, Veronika

Lilly, Eli

Green, Robert C. ^{[10
]}

Montine, Tom ^{[12
,23
]}

Petersen, Ronald ^{[5
]}

Aisen, Paul ^{[4
]}

Jimenez, Gustavo ^{[8
]}

Donohue, Michael ^{[8
,24
]}

Gessert, Devon ^{[8
]}

Harless, Kelly ^{[8
]}

Salazar, Jennifer ^{[8
]}

Cabrera, Yuliana ^{[8
]}

Walter, Sarah ^{[8
]}

Hergesheimer, Lindsey ^{[8
]}

Beckett, Laurel ^{[9
]}

Harvey, Danielle

Donohue, Michael ^{[8
,24
]}

Jack, Clifford R., Jr. ^{[5
]}

Bernstein, Matthew ^{[5
]}

机构：

[1] LMU, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Feodor Lynen Str 17, D-81377 Munich, Germany

[2] Ist Nazl Fis Nucl, Sez Bari, Bari, Italy

[3] UC San Francisco, San Francisco, CA USA

[4] Univ Calif San Diego, San Diego, CA 92093 USA

[5] Mayo Clin, Rochester, NY 14603 USA

[6] Univ Calif Berkeley, Berkeley, CA 94720 USA

[7] UPenn, Philadelphia, PA 19104 USA

[8] USC, Los Angeles, CA 90089 USA

[9] Univ Calif Davis, Davis, CA 95616 USA

[10] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA

[11] Indiana Univ, Bloomington, IN 47405 USA

[12] Washington Univ, St Louis, MO 63130 USA

[13] Prevent Alzheimers Dis 2020, Rockville, MD 20850 USA

[14] Siemens, D-80333 Munich, Germany

[15] Univ Pittsburgh, Pittsburgh, PA 15260 USA

[16] Cornell Univ, Weill Cornell Med Coll, New York, NY 10065 USA

[17] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY 10461 USA

[18] Ad Drug Discovery Fdn, New York, NY 10019 USA

[19] Acumen Pharmceut, Livermore, CA USA

[20] Northwestern Univ, Evanston, IL 60208 USA

[21] NIMH, Rockville, MD 20857 USA

[22] Brown Univ, Providence, RI 02912 USA

[23] Univ Washington, Seattle, WA 98195 USA

[24] Univ Calif San Diego, La Jolla, CA USA

[25] Univ London, London, England

[26] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA

[27] UCSF, MRI, San Francisco, CA USA

[28] Univ Michigan, Ann Arbor, MI 48109 USA

[29] Univ Utah, Salt Lake City, UT 84112 USA

[30] Banner Alzheimers Inst, Phoenix, AZ USA

[31] UPenn Sch Med, Philadelphia, PA USA

[32] UC Irvine, Irvine, CA USA

[33] NIA, Bethesda, MD 20892 USA

[34] Johns Hopkins Univ, Baltimore, MD 21218 USA

[35] Richard Frank Consulting, Sacramento, CA USA

[36] Oregon Hlth & Sci Univ, Portland, OR 97201 USA

[37] Univ Calif San Diego, La Jolla, CA 92093 USA

[38] Baylor Coll Med, Houston, TX 77030 USA

[39] Columbia Univ, Med Ctr, New York, NY 10027 USA

[40] Univ Alabama Birmingham, Birmingham, AL USA

[41] Mt Sinai Sch Med, New York, NY USA

[42] Rush Univ, Med Ctr, Chicago, IL 60612 USA

[43] Wien Ctr, Vienna, Austria

[44] NYU, New York, NY 10003 USA

[45] Duke Univ, Med Ctr, Durham, NC 27706 USA

[46] Univ Kentucky, Lexington, KY 40506 USA

[47] Univ Rochester, Med Ctr, Rochester, NY 14627 USA

[48] Univ Calif Irvine, IMIND, Irvine, CA 92717 USA

[49] Univ Texas Southwestern Med Sch, Dallas, TX USA

[50] Emory Univ, Atlanta, GA 30332 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

ALZHEIMERS-DISEASE; COGNITIVE RESERVE; GENE-EXPRESSION; BRAIN; PATHOLOGY; CONNECTIVITY; DECLINE; PROTEIN; RISK; NEURODEGENERATION;

D O I：

10.1038/s41467-019-09564-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

共 8 条

[1] The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory
Nicolai Franzmeier
Anna Rubinski
Julia Neitzel
Michael Ewers
[J]. Nature Communications, 10
[2] The BIN1 rs744373 Alzheimer's disease risk SNP is associated with faster Aβ-associated tau accumulation and cognitive decline
Franzmeier, Nicolai
Ossenkoppele, Rik
Brendel, Matthias
Rubinski, Anna
Smith, Ruben
Kumar, Atul
Mattsson-Carlgren, Niklas
Strandberg, Olof
Duering, Marco
Buerger, Katharina
Dichgans, Martin
Hansson, Oskar
Ewers, Michael
[J]. ALZHEIMERS & DEMENTIA, 2022, 18 (01) : 103 - 115
[3] Lack of association between bridging integrator 1 (BIN1) rs744373 polymorphism and tau-PET load in cognitively intact older adults
Schaeverbeke, Jolien
Luckett, Emma S.
Gabel, Silvy
Reinartz, Mariska
De Meyer, Steffi
Cleynen, Isabelle
Sleegers, Kristel
Van Broeckhoven, Christine
Bormans, Guy
Serdons, Kim
Van Laere, Koen
Dupont, Patrick
Vandenberghe, Rik
[J]. ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS, 2022, 8 (01)
[4] BIN1 rs744373 Variant Is Significantly Associated with Alzheimer's Disease in Caucasian but Not East Asian Populations
Han, Zhifa
Wang, Tao
Tian, Rui
Zhou, Wenyang
Wang, Pingping
Ren, Peng
Zong, Jian
Hu, Yang
Jin, Shuilin
Jiang, Qinghua
[J]. INTELLIGENT COMPUTING THEORIES AND APPLICATION, PT I, 2018, 10954 : 520 - 526
[5] BIN1 gene rs744373 polymorphism contributes to Alzheimer's disease in East Asian population
Liu, Guiyou
Zhang, Shuyan
Cai, Zhiyou
Li, You
Cui, Lili
Ma, Guoda
Jiang, Yongshuai
Zhang, Liangcai
Feng, Rennan
Liao, Mingzhi
Chen, Zugen
Zhao, Bin
Li, Keshen
[J]. NEUROSCIENCE LETTERS, 2013, 544 : 47 - 51
[6] BIN1 rs744373 located in enhancers of brain tissues upregulates BIN1 mRNA expression, thereby leading to Alzheimer's disease
Qiu, Shizheng
Hu, Yang
Cheng, Liang
[J]. ALZHEIMERS & DEMENTIA, 2022, 18 (08) : 1587 - 1588
[7] BIN1 rs744373 variant shows different association with Alzheimer's disease in Caucasian and Asian populations
Han, Zhifa
Wang, Tao
Tian, Rui
Zhou, Wenyang
Wang, Pingping
Ren, Peng
Zong, Jian
Hu, Yang
Jin, Shuilin
Jiang, Qinghua
[J]. BMC BIOINFORMATICS, 2019, 20 (01)
[8] BIN1 rs744373 variant shows different association with Alzheimer’s disease in Caucasian and Asian populations
Zhifa Han
Tao Wang
Rui Tian
Wenyang Zhou
Pingping Wang
Peng Ren
Jian Zong
Yang Hu
Shuilin Jin
Qinghua Jiang
[J]. BMC Bioinformatics, 20

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