Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report

被引：363

作者：

Arboleda-Velasquez, Joseph F. ^{[1
,2
,3
,4
]}

Lopera, Francisco ^{[3
]}

O'Hare, Michael ^{[1
,2
]}

Delgado-Tirado, Santiago ^{[1
,2
]}

Marino, Claudia ^{[1
,2
]}

Chmielewska, Natalia ^{[1
,2
,4
]}

Saez-Torres, Kahira L. ^{[1
,2
]}

Amarnani, Dhanesh ^{[1
,2
]}

Schultz, Aaron P. ^{[5
,6
]}

Sperling, Reisa A. ^{[5
,6
,7
]}

Leyton-Cifuentes, David ^{[1
,2
,8
]}

Chen, Kewei ^{[9
,10
,11
]}

Baena, Ana ^{[3
]}

Aguillon, David ^{[3
]}

Rios-Romenets, Silvia ^{[3
]}

Giraldo, Margarita ^{[3
]}

Guzman-Velez, Edmarie ^{[5
,12
]}

Norton, Daniel J. ^{[5
,12
,13
]}

Pardilla-Delgado, Enmanuelle ^{[5
,12
]}

Artola, Arabiye ^{[5
,12
]}

Sanchez, Justin S. ^{[5
]}

Acosta-Uribe, Juliana ^{[14
]}

Lalli, Matthew ^{[14
]}

Kosik, Kenneth S. ^{[14
]}

Huentelman, Matthew J. ^{[15
]}

Zetterberg, Henrik ^{[16
,17
,18
,19
]}

Blennow, Kaj ^{[16
,17
]}

Reiman, Rebecca A. ^{[15
]}

Luo, Ji ^{[9
]}

Chen, Yinghua ^{[9
]}

Thiyyagura, Pradeep ^{[9
]}

Su, Yi ^{[9
]}

Jun, Gyungah R. ^{[20
]}

Naymik, Marcus ^{[15
]}

Gai, Xiaowu ^{[21
,22
]}

Bootwalla, Moiz ^{[21
]}

Ji, Jianling ^{[21
,22
]}

Shen, Lishuang ^{[21
]}

Miller, John B. ^{[2
,23
]}

Kim, Leo A. ^{[1
,2
]}

Tariot, Pierre N. ^{[9
,10
]}

Johnson, Keith A. ^{[5
,6
,7
,24
]}

Reiman, Eric M. ^{[9
,10
,11
,15
]}

Quiroz, Yakeel T. ^{[3
,6
,12
]}

机构：

[1] Harvard Med Sch, Schepens Eye Res Inst, Mass Eye & Ear, Boston, MA 02115 USA

[2] Harvard Med Sch, Dept Ophthalmol, Boston, MA 02115 USA

[3] Univ Antioquia, Grp Neurociencias Antioquia, Medellin, Colombia

[4] Boston Coll, Boston, MA USA

[5] Massachusetts Gen Hosp, Boston, MA 02114 USA

[6] Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA

[7] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA

[8] Univ Escuela Ingn Antioquia EIA, Medellin, Colombia

[9] Banner Alzheimers Inst, Phoenix, AZ USA

[10] Univ Arizona, Tucson, AZ USA

[11] Arizona State Univ, Tempe, AZ USA

[12] Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA

[13] Gordon Coll, Dept Psychol, Wenham, MA USA

[14] Univ Calif Santa Barbara, Dept Mol Cellular Dev Biol, Neurosci Res Inst, Santa Barbara, CA 93106 USA

[15] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA

[16] Sahlgrens Univ Hosp, Clin Neurochemistry Lab, Molndal, Sweden

[17] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden

[18] UCL, Queen Sq Inst Neurol, Dept Neurodegenerat Dis, London, England

[19] UCL, UK Dementia Res Inst, London, England

[20] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA

[21] Childrens Hosp Los Angeles, Dept Pathol & Lab Med, Ctr Personalized Med, Los Angeles, CA 90027 USA

[22] Univ Southern Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90007 USA

[23] Harvard Med Sch, Mass Eye & Ear, Boston, MA 02115 USA

[24] Harvard Med Sch, Dept Radiol, Boston, MA 02115 USA

来源：

NATURE MEDICINE | 2019年 / 25卷 / 11期

基金：

美国国家卫生研究院;

关键词：

HUMAN APOLIPOPROTEIN-E; AGE-OF-ONSET; BINDING; VARIANTS; MUTATION; ALLELE;

D O I：

10.1038/s41591-019-0611-3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.

引用

页码：1680 / +

页数：10

共 35 条

[1] Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer's disease: a retrospective cohort study [J].

Acosta-Baena, Natalia ;

Sepulveda-Falla, Diego ;

Mario Lopera-Gomez, Carlos ;

Cesar Jaramillo-Elorza, Mario ;

Moreno, Sonia ;

Camilo Aguirre-Acevedo, Daniel ;

Saldarriaga, Amanda ;

Lopera, Francisco .

LANCET NEUROLOGY, 2011, 10 (03) :213-220

[2] Validity and reliability of the CERAD-Col neuropsychological battery [J].

Aguirre-Acevedo, D. C. ;

Gomez, R. D. ;

Moreno, S. ;

Henao-Arboleda, E. ;

Motta, M. ;

Munoz, C. ;

Arana, A. ;

Pineda, D. A. ;

Lopera, F. .

REVISTA DE NEUROLOGIA, 2007, 45 (11) :655-660

[3] Amyloid-β Associated Cortical Thinning in Clinically Normal Elderly [J].

Becker, J. Alex ;

Hedden, Trey ;

Carmasin, Jeremy ;

Maye, Jacqueline ;

Rentz, Dorene M. ;

Putcha, Deepti ;

Fischl, Bruce ;

Greve, Douglas N. ;

Marshall, Gad A. ;

Salloway, Stephen ;

Marks, Donald ;

Buckner, Randy L. ;

Sperling, Reisa A. ;

Johnson, Keith A. .

ANNALS OF NEUROLOGY, 2011, 69 (06) :1032-1042

[4] Diagnostic criteria for neuropathologic assessment of Alzheimer's disease [J].

Braak, H ;

Braak, E .

NEUROBIOLOGY OF AGING, 1997, 18 (04) :S85-S88

[5]

Braak H, 2006, J ALZHEIMERS DIS, V9, P35

[6] Integrating single-cell transcriptomic data across different conditions, technologies, and species [J].

Butler, Andrew ;

Hoffman, Paul ;

Smibert, Peter ;

Papalexi, Efthymia ;

Satija, Rahul .

NATURE BIOTECHNOLOGY, 2018, 36 (05) :411-+

[7] Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F-18]-T807 [J].

Chien, David T. ;

Bahri, Shadfar ;

Szardenings, A. Katrin ;

Walsh, Joseph C. ;

Mu, Fanrong ;

Su, Min-Ying ;

Shankle, William R. ;

Elizarov, Arkadij ;

Kolb, Hartmuth C. .

JOURNAL OF ALZHEIMERS DISEASE, 2013, 34 (02) :457-468

[8] PROTECTIVE EFFECT OF APOLIPOPROTEIN-E TYPE-2 ALLELE FOR LATE-ONSET ALZHEIMER-DISEASE [J].

CORDER, EH ;

SAUNDERS, AM ;

RISCH, NJ ;

STRITTMATTER, WJ ;

SCHMECHEL, DE ;

GASKELL, PC ;

RIMMLER, JB ;

LOCKE, PA ;

CONNEALLY, PM ;

SCHMADER, KE ;

SMALL, GW ;

ROSES, AD ;

HAINES, JL ;

PERICAKVANCE, MA .

NATURE GENETICS, 1994, 7 (02) :180-184

[9] A scalable, fully automated process for construction of sequence-ready human exome targeted capture libraries [J].

Fisher, Sheila ;

Barry, Andrew ;

Abreu, Justin ;

Minie, Brian ;

Nolan, Jillian ;

Delorey, Toni M. ;

Young, Geneva ;

Fennell, Timothy J. ;

Allen, Alexander ;

Ambrogio, Lauren ;

Berlin, Aaron M. ;

Blumenstiel, Brendan ;

Cibulskis, Kristian ;

Friedrich, Dennis ;

Johnson, Ryan ;

Juhn, Frank ;

Reilly, Brian ;

Shammas, Ramy ;

Stalker, John ;

Sykes, Sean M. ;

Thompson, Jon ;

Walsh, John ;

Zimmer, Andrew ;

Zwirko, Zac ;

Gabriel, Stacey ;

Nicol, Robert ;

Nusbaum, Chad .

GENOME BIOLOGY, 2011, 12 (01)

[10] Associations Between Biomarkers and Age in the Presenilin 1 E280A Autosomal Dominant Alzheimer Disease Kindred A Cross-sectional Study [J].

Fleisher, Adam S. ;

Chen, Kewei ;

Quiroz, Yakeel T. ;

Jakimovich, Laura J. ;

Gutierrez Gomez, Madelyn ;

Langois, Carolyn M. ;

Langbaum, Jessica B. S. ;

Roontiva, Auttawut ;

Thiyyagura, Pradeep ;

Lee, Wendy ;

Ayutyanont, Napatkamon ;

Lopez, Liliana ;

Moreno, Sonia ;

Munoz, Claudia ;

Tirado, Victoria ;

Acosta-Baena, Natalia ;

Fagan, Anne M. ;

Giraldo, Margarita ;

Garcia, Gloria ;

Huentelman, Matthew J. ;

Tariot, Pierre N. ;

Lopera, Francisco ;

Reiman, Eric M. .

JAMA NEUROLOGY, 2015, 72 (03) :316-324

← 1 2 3 4 →