Refining Risk for Alzheimer's Disease Among Heterozygous APOE ε4 Carriers

被引：4

作者：

Patel, Smita ^{[1
]}

Wei, Jun ^{[2
]}

Shi, Zhuqing ^{[2
]}

Rifkin, Andrew S. ^{[2
]}

Zheng, S. Lilly ^{[2
]}

Gelfman, Elizabeth ^{[3
]}

Duggan, David ^{[4
]}

Helfand, Brian T. ^{[2
,5
]}

Hulick, Peter J. ^{[6
]}

Xu, Jianfeng ^{[2
,5
]}

机构：

[1] NorthShore Univ HlthSyst, Dept Neurol, Evanston, IL USA

[2] NorthShore Univ HlthSyst, Program Personalized Canc Care, Evanston, IL USA

[3] Northwestern Feinberg Sch Med, Chicago, IL USA

[4] City Hope Natl Med Ctr, Translat Genom Res Inst, Phoenix, AZ USA

[5] Univ Chicago, Pritzker Sch Med, Chicago, IL USA

[6] NorthShore Univ HlthSyst, Neaman Ctr Personalized Med, Evanston, IL USA

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2023年 / 94卷 / 02期

关键词：

Alzheimer's disease; APOE; genetic counseling; polygenic risk score; UK Biobank; APOLIPOPROTEIN-E; DISCLOSURE; GENOTYPE;

D O I：

10.3233/JAD-230156

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

In a large population-based cohort, we show not all heterozygous APOE epsilon 4 carriers are at increased risk for Alzheimer's disease (AD); a significantly higher AD proportion was only found for epsilon 3/epsilon 4, not epsilon 2/epsilon 4. Among epsilon 3/epsilon 4 carriers (24% in the cohort), the AD proportion differed considerably by polygenic risk score (PRS). In particular, the AD proportion was lower than the entire cohort for subjects in the bottom 20-percentile PRS and was higher than that of homozygous epsilon 4 carriers for subjects at the top 5th-percentile PRS. Family history was no longer a significant predictor of AD risk after adjusting APOE and PRS.

引用

页码：483 / 489

页数：7

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[21] Polygenic risk scores for Alzheimer's disease are related to dementia risk in APOE e4 negatives [J].

Najar, Jenna ;

van der Lee, Sven J. ;

Joas, Erik ;

Wetterberg, Hanna ;

Hardy, John ;

Guerreiro, Rita ;

Bras, Jose ;

Waern, Margda ;

Kern, Silke ;

Zetterberg, Henrik ;

Blennow, Kaj ;

Skoog, Ingmar ;

Zettergren, Anna .

ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING, 2021, 13 (01)

[22] APOE and Alzheimer's disease and related dementias risk among 12,221 Hispanics/Latinos [J].

Barral, Sandra ;

Yang, Zikun ;

Phillips, Nicole ;

Barber, Robert C. ;

Brickman, Adam M. ;

Honig, Lawrence S. ;

Cieza, Basilio ;

Reyes-Dumeyer, Dolly ;

Mayeux, Richard ;

Rajabli, Farid ;

Cuccaro, Michael L. ;

Vance, Jeffery M. ;

Arango, Silvia Mejia ;

Samper-Ternent, Rafael ;

Obregon, Alejandra Michaels ;

Montesinos, Rosa ;

Soto-Anari, Marcio ;

Duran, Juan Carlos ;

Cusicanqui, Maria ;

Velazquez, Ivonne Z. Jimenez ;

Marca, Victoria ;

Illanes-Manrique, Maryenela ;

Cornejo-Olivas, Mario ;

Pericak-Vance, Margaret ;

Wong, Rebeca ;

O'Bryant, Sid ;

Custodio, Nilton ;

Tosto, Giuseppe .

ALZHEIMERS & DEMENTIA, 2025, 21 (04)

[23] Impact of sex and APOE4 on cerebral amyloid angiopathy in Alzheimer's disease [J].

Shinohara, Mitsuru ;

Murray, Melissa E. ;

Frank, Ryan D. ;

Shinohara, Motoko ;

DeTure, Michael ;

Yamazaki, Yu ;

Tachibana, Masaya ;

Atagi, Yuka ;

Davis, Mary D. ;

Liu, Chia-Chen ;

Zhao, Na ;

Painter, Meghan M. ;

Petersen, Ronald C. ;

Fryer, John D. ;

Crook, Julia E. ;

Dickson, Dennis W. ;

Bu, Guojun ;

Kanekiyo, Takahisa .

ACTA NEUROPATHOLOGICA, 2016, 132 (02) :225-234

[24] SREBP-1a polymorphism influences the risk of Alzheimer's disease in carriers of the ApoE4 allele [J].

Spell, C ;

Kölsch, H ;

Lütjohann, D ;

Kerksiek, A ;

Hentschel, F ;

Damian, M ;

von Bergmann, K ;

Rao, ML ;

Maier, W ;

Heun, R .

DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 2004, 18 (3-4) :245-249

[25] APOE ε4 and REM Sleep Behavior Disorder as Risk Factors for Sundown Syndrome in Alzheimer's Disease [J].

Pyun, Jung-Min ;

Kang, Min Ju ;

Yun, Younghwa ;

Park, Young Ho ;

Kim, SangYun .

JOURNAL OF ALZHEIMERS DISEASE, 2019, 69 (02) :521-528

[26] Polymorphisms of Proinflammatory Cytokines in Relation to APOE Epsilon 4 and Risk of Alzheimer's Disease in the Lithuanian Population [J].

Psemeneckiene, Greta ;

Petrikonis, Kestutis ;

Rastenyte, Daiva .

MEDICINA-LITHUANIA, 2019, 55 (10)

[27] Cortical Transcriptional Profiles in APOE4 Carriers with Alzheimer's Disease: Patterns of Protection and Degeneration [J].

Conejero-Goldberg, Concepcion ;

Hyde, Thomas M. ;

Chen, Shufen ;

Herman, Mary M. ;

Kleinman, Joel E. ;

Davies, Peter ;

Goldberg, Terry E. .

JOURNAL OF ALZHEIMERS DISEASE, 2015, 48 (04) :969-978

[28] Functional connectivity among brain regions affected in Alzheimer's disease is associated with CSF TNF-α in APOE4 carriers [J].

Contreras, Joey Annette ;

Aslanyan, Vahan ;

Sweeney, Melanie D. ;

Sanders, Lianne M. J. ;

Sagare, Abhay P. ;

Zlokovic, Berislav, V ;

Toga, Arthur W. ;

Han, S. Duke ;

Morris, John C. ;

Fagan, Anne ;

Massoumzadeh, Parinaz ;

Benzinger, Tammie L. ;

Pa, Judy .

NEUROBIOLOGY OF AGING, 2020, 86 :112-122

[29] Do Cardiometabolic Risk Factors Influence Amyloid, Tau, and Neuronal Function in APOE4 Carriers and Non-Carriers in Alzheimer's Disease Trajectory? [J].

Femminella, Grazia Daniela ;

Taylor-Davies, Genevieve ;

Scott, James ;

Edison, Paul .

JOURNAL OF ALZHEIMERS DISEASE, 2018, 64 (03) :981-993

[30] Higher Level of Mismatch in APOE ε4 Carriers for Amyloid-Beta Peptide Alzheimer's Disease Biomarkers in Cerebrospinal Fluid [J].

Vogelgsang, Jonathan ;

Vukovich, Ruth ;

Wedekind, Dirk ;

Wiltfang, Jens .

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