- Record: found
- Abstract: found
- Article: found
Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study
research-article
Author(s):
Eric M. Reiman
1
,
2
,
3
,
4
,
,
Joseph F. Arboleda-Velasquez
5 ,
Yakeel T. Quiroz
6 ,
Matthew J. Huentelman
4 ,
Thomas G. Beach
1 ,
Richard J. Caselli
7 ,
Yinghua Chen
1 ,
Yi Su
1 ,
Amanda J. Myers
8 ,
John Hardy
9 ,
Jean Paul Vonsattel
10 ,
Steven G. Younkin
11 ,
David A. Bennett
12 ,
Philip L. De Jager
13 ,
Eric B. Larson
14 ,
Paul K. Crane
15 ,
C. Dirk Keene
16 ,
M. Ilyas Kamboh
17 ,
Julia K. Kofler
18 ,
Linda Duque
19 ,
John R. Gilbert
20 ,
Harry E. Gwirtsman
21 ,
Joseph D. Buxbaum
22 ,
Dennis W. Dickson
23 ,
Matthew P. Frosch
24 ,
Bernardino F. Ghetti
25 ,
Kathryn L. Lunetta
26 ,
Li-San Wang
27 ,
Bradley T. Hyman
28 ,
Walter A. Kukull
29 ,
Tatiana Foroud
30 ,
Jonathan L. Haines
31 ,
Richard P. Mayeux
32 ,
Margaret A. Pericak-Vance
20 ,
Julie A. Schneider
12 ,
John Q. Trojanowski
27 ,
Lindsay A. Farrer
26
,
33
,
34
,
35 ,
Gerard D. Schellenberg
27 ,
Gary W. Beecham
20 ,
Thomas J. Montine
36 ,
Gyungah R. Jun
33 ,
The Alzheimer’s Disease Genetics Consortium
Publication date (Electronic):
3 February 2020
Journal:
Nature Communications
Publisher:
Nature Publishing Group UK
There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer’s dementia, while the APOE2 allele is associated with a lower risk of Alzheimer’s dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk. We generated Alzheimer’s dementia odds ratios and other findings in more than 5,000 clinically characterized and neuropathologically characterized Alzheimer’s dementia cases and controls. APOE2/2 was associated with a low Alzheimer’s dementia odds ratios compared to APOE2/3 and 3/3, and an exceptionally low odds ratio compared to APOE4/4, and the impact of APOE2 and APOE4 gene dose was significantly greater in the neuropathologically confirmed group than in more than 24,000 neuropathologically unconfirmed cases and controls. Finding and targeting the factors by which APOE and its variants influence Alzheimer’s disease could have a major impact on the understanding, treatment and prevention of the disease.
Abstract
APOE is the major genetic risk factor for Alzheimer’s disease. In a large number of neuropathologically confirmed cases and controls, the impact of different APOE genotypes on Alzheimer’s dementia risk was greater than previously thought and APOE2 homozygotes had an exceptionally low risk.
Related collections
Most cited references32
- Record: found
- Abstract: found
- Article: not found
Neuropathological stageing of Alzheimer-related changes
Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.
- Record: found
- Abstract: found
- Article: found
Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
Brian Kunkle, Benjamin Grenier-Boley, Rebecca Sims … (2019)
Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.
- Record: found
- Abstract: found
- Article: not found
ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy
Yang Shi, Shane Liddelow, Scott T. Smith … (2017)
APOE4 is the strongest genetic risk factor for late-onset Alzheimer disease. ApoE4 increases brain amyloid-β pathology relative to other ApoE isoforms. However, whether APOE independently influences tau pathology, the other major proteinopathy of Alzheimer disease and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human ApoE knock-in (KI) or ApoE knockout (KO) background, here we show that P301S/E4 mice have significantly higher tau levels in the brain and a greater extent of somatodendritic tau redistribution by three months of age compared with P301S/E2, P301S/E3, and P301S/EKO mice. By nine months of age, P301S mice with different ApoE genotypes display distinct phosphorylated tau protein (p-tau) staining patterns. P301S/E4 mice develop markedly more brain atrophy and neuroinflammation than P301S/E2 and P301S/E3 mice, whereas P301S/EKO mice are largely protected from these changes. In vitro, E4-expressing microglia exhibit higher innate immune reactivity after lipopolysaccharide treatment. Co-culturing P301S tau-expressing neurons with E4-expressing mixed glia results in a significantly higher level of tumour-necrosis factor-α (TNF-α) secretion and markedly reduced neuronal viability compared with neuron/E2 and neuron/E3 co-cultures. Neurons co-cultured with EKO glia showed the greatest viability with the lowest level of secreted TNF-α. Treatment of P301S neurons with recombinant ApoE (E2, E3, E4) also leads to some neuronal damage and death compared with the absence of ApoE, with ApoE4 exacerbating the effect. In individuals with a sporadic primary tauopathy, the presence of an ε4 allele is associated with more severe regional neurodegeneration. In individuals who are positive for amyloid-β pathology with symptomatic Alzheimer disease who usually have tau pathology, ε4-carriers demonstrate greater rates of disease progression. Our results demonstrate that ApoE affects tau pathogenesis, neuroinflammation, and tau-mediated neurodegeneration independently of amyloid-β pathology. ApoE4 exerts a ‘toxic’ gain of function whereas the absence of ApoE is protective.
Author and article information
Contributors
Eric M. Reiman:
ORCID: http://orcid.org/0000-0002-0705-3696
eric.reiman@bannerhealth.com
Journal
Journal ID (nlm-ta): Nat Commun
Journal ID (iso-abbrev): Nat Commun
Title:
Nature Communications
Publisher:
Nature Publishing Group UK
(London
)
ISSN
(Electronic):
2041-1723
Publication date
(Electronic):
3
February
2020
Publication date PMC-release: 3
February
2020
Publication date Collection: 2020
Volume: 11
Electronic Location Identifier: 667
Affiliations
[1
]ISNI 0000 0004 0406 4925, GRID grid.418204.b, Banner Alzheimer’s Institute and Arizona Alzheimer’s Consortium, ; 901 E Willetta Street, Phoenix, AZ 85006 USA
[2
]ISNI 0000 0001 2168 186X, GRID grid.134563.6, University of Arizona, ; 714 E Van Buren Street, Phoenix, AZ 85006 USA
[3
]ISNI 0000 0001 2151 2636, GRID grid.215654.1, Arizona State University, ; 522 N Central Avenue, Phoenix, AZ 85004 USA
[4
]ISNI 0000 0004 0507 3225, GRID grid.250942.8, Neurogenomics Division, , Translational Genomics Research Institute and Arizona Alzheimer’s Consortium, ; 445 N Fifth Street, Phoenix, AZ 85004 USA
[5
]ISNI 000000041936754X, GRID grid.38142.3c, Schepens Eye Research Institute of Mass Eye and Ear and the Department of Ophthalmology
at Harvard Medical School, ; 20 Staniford Street, Boston, MA 02114 USA
[6
]ISNI 0000 0004 0386 9924, GRID grid.32224.35, Departments of Psychiatry and Neurology, , Massachusetts General Hospital and Harvard Medical School, ; 55 Fruit Street, Boston, MA 02114 USA
[7
]ISNI 0000 0000 8875 6339, GRID grid.417468.8, Mayo Clinic, ; 13400 E Shea Boulevard, Scottsdale, AZ 85259 USA
[8
]ISNI 0000 0004 1936 8606, GRID grid.26790.3a, Department of Psychiatry and Behavioral Science, , University of Miami Miller School of Medicine, ; 1120 NW 14th Street, Miami, FL 33136 USA
[9
]ISNI 0000000121901201, GRID grid.83440.3b, Department of Molecular Neuroscience, UCL, , Institute of Neurology, ; Queen Square, London, WC1N 3BG UK
[10
]ISNI 0000 0000 8499 1112, GRID grid.413734.6, New York Brain Bank and Department of Pathology, , New York-Presbyterian Hospital at Columbia University Medical Center, ; 630 West 168th Street, New York, NY 10032 USA
[11
]ISNI 0000 0004 0443 9942, GRID grid.417467.7, Departments of Neuroscience and Neurology, , Mayo Clinic, ; 4500 San Pablo Road, Jacksonville, FL 32224 USA
[12
]ISNI 0000 0001 0705 3621, GRID grid.240684.c, Departments of Neurological Sciences and Pathology (Neuropathology), and Rush Alzheimer’s
Disease Center, , Rush University Medical Center, ; 1725 W Harrison Street, Chicago, IL 60612 USA
[13
]ISNI 0000 0001 2285 2675, GRID grid.239585.0, Department of Neurology, Center for Translational and Computational Neuroimmunology,
, Columbia University Medical Center, ; 710 West 168th Street, New York, NY 10032 USA
[14
]ISNI 0000 0004 0615 7519, GRID grid.488833.c, Kaiser Permanente Washington Health Research Institute, ; 1730 Minor Avenue, Seattle, WA 98101 USA
[15
]ISNI 0000000122986657, GRID grid.34477.33, Department of Medicine, , University of Washington, ; 1959 NE Pacific Street, Seattle, WA 98198 USA
[16
]ISNI 0000000122986657, GRID grid.34477.33, Department of Pathology, , University of Washington, ; 1959 NE Pacific Street, Seattle, WA 98198 USA
[17
]ISNI 0000 0004 1936 9000, GRID grid.21925.3d, Department of Human Genetics, Alzheimer’s Disease Research Center, , University of Pittsburgh, ; 200 Lothrop Street, Pittsburgh, PA 15213 USA
[18
]ISNI 0000 0004 1936 9000, GRID grid.21925.3d, Department of Pathology (Neuropathology), , University of Pittsburgh, ; 200 Lothrop Street, Pittsburgh, PA 15213 USA
[19
]ISNI 0000 0004 1936 8606, GRID grid.26790.3a, Department of Neurology, , University of Miami, ; 1120 NW 14th Street, Miami, FL 33136 USA
[20
]ISNI 0000 0004 1936 8606, GRID grid.26790.3a, John P. Hussman Institute for Human Genomics, Department of Human Genetics, and Dr.
John T. Macdonald Foundation, , University of Miami, ; 1501 NW 10th Avenue, Miami, FL 33136 USA
[21
]ISNI 0000 0001 2264 7217, GRID grid.152326.1, Department of Psychiatry, , Vanderbilt University, ; 1601 23rd Avenue South, Nashville, TN 37212 USA
[22
]ISNI 0000 0001 0670 2351, GRID grid.59734.3c, Departments of Psychiatry, Neuroscience and Genetics and Genomic Sciences, , Mount Sinai School of Medicine, ; 1468 Madison Avenue, New York, NY 10029 USA
[23
]ISNI 0000 0004 0443 9942, GRID grid.417467.7, Department of Neuroscience, , Mayo Clinic, ; 4500 San Pablo Road, Jacksonville, FL 32224 USA
[24
]ISNI 0000 0004 0386 9924, GRID grid.32224.35, C.S. Kubik Laboratory for Neuropathology, , Massachusetts General Hospital, ; 114 16th Street, Charlestown, MA 02129 USA
[25
]ISNI 0000 0001 2287 3919, GRID grid.257413.6, Department of Pathology and Laboratory Medicine, , Indiana University, ; 340 West 10th Street, Indianapolis, IN 46202 USA
[26
]ISNI 0000 0004 1936 7558, GRID grid.189504.1, Department of Biostatistics, , Boston University School of Public Health, ; 801 Massachusetts Avenue, Boston, MA 02118 USA
[27
]ISNI 0000 0004 1936 8972, GRID grid.25879.31, Department of Pathology and Laboratory Medicine, , University of Pennsylvania Perelman School of Medicine, ; 3400 Spruce Street, Philadelphia, PA 19104 USA
[28
]ISNI 0000 0004 0386 9924, GRID grid.32224.35, Department of Neurology, , Massachusetts General Hospital and Harvard Medical School, ; 55 Fruit Street, Boston, MA 02114 USA
[29
]ISNI 0000000122986657, GRID grid.34477.33, Department of Epidemiology, , University of Washington, ; 1959 NE Pacific Street, Seattle, WA 98195 USA
[30
]ISNI 0000 0001 2287 3919, GRID grid.257413.6, Department of Medical and Molecular Genetics, , Indiana University, ; 410W 10th Street, Indianapolis, IN 46202 USA
[31
]ISNI 0000 0001 2164 3847, GRID grid.67105.35, Institute for Computational Biology and Department of Population and Quantitative
Health Sciences, , Case Western Reserve University, ; 10900 Euclid Avenue, Cleveland, OH 44106 USA
[32
]ISNI 0000000419368729, GRID grid.21729.3f, Taub Institute on Alzheimer’s Disease and the Aging Brain, Gertrude H. Sergievsky
Center Department of Neurology, , Columbia University, ; 710 West 168th Street, New York, NY 10032 USA
[33
]ISNI 0000 0004 0367 5222, GRID grid.475010.7, Biomedical Genetics Section, Department of Medicine, , Boston University School of Medicine, ; 72 East Concord Street, Boston, MA 02118 USA
[34
]ISNI 0000 0004 0367 5222, GRID grid.475010.7, Department of Neurology, , Boston University School of Medicine, ; 72 East Concord Street, Boston, MA 02118 USA
[35
]ISNI 0000 0004 1936 7558, GRID grid.189504.1, Department of Epidemiology, , Boston University School of Public Health, ; 715 Albany Street, Boston, MA 02118 USA
[36
]ISNI 0000000419368956, GRID grid.168010.e, Department of Pathology, , Stanford University, ; 300 Pasteur Drive, Stanford, CA 94305 USA
[37
]ISNI 0000 0004 1936 8438, GRID grid.266539.d, Department of Epidemiology, College of Public Health, Sanders-Brown Center on Aging,
, University of Kentucky, ; Lexington, Kentucky USA
[38
]ISNI 0000 0000 9482 7121, GRID grid.267313.2, Department of Psychiatry, , University of Texas Southwestern Medical Center, ; Dallas, TX USA
[39
]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Department of Neurology, , Johns Hopkins University, ; Baltimore, MD USA
[40
]ISNI 0000000086837370, GRID grid.214458.e, Department of Neurology, , University of Michigan, ; Ann Arbor, MI USA
[41
]ISNI 0000 0004 0419 7525, GRID grid.413800.e, Geriatric Research, Education and Clinical Center (GRECC), , VA Ann Arbor Healthcare System (VAAAHS), ; Ann Arbor, MI USA
[43
]ISNI 0000 0001 2287 3919, GRID grid.257413.6, Department of Radiology, , Indiana University, ; Indianapolis, IA USA
[44
]ISNI 0000 0001 2287 3919, GRID grid.257413.6, Department of Medical and Molecular Genetics, , Indiana University, ; Indianapolis, IA USA
[45
]ISNI 0000 0001 2287 3919, GRID grid.257413.6, Indian Alzheimer’s Disease Center, , Indiana University, ; Indianapolis, IA USA
[46
]ISNI 0000 0001 2287 3919, GRID grid.257413.6, Department of Neurology, , Indiana University, ; Indianapolis, IA USA
[47
]ISNI 0000 0004 1936 7961, GRID grid.26009.3d, Department of Psychiatry and Behavioral Sciences, , Duke University, ; Durham, NC USA
[48
]ISNI 0000 0004 1936 8972, GRID grid.25879.31, Department of Psychiatry, , University of Pennsylvania Perelman School of Medicine, ; Philadelphia, PA USA
[49
]ISNI 0000 0001 0701 8607, GRID grid.28803.31, Geriatric Research, Education and Clinical Center (GRECC), , University of Wisconsin, ; Madison, WI USA
[50
]ISNI 0000 0001 0701 8607, GRID grid.28803.31, Department of Medicine, , University of Wisconsin, ; Madison, WI USA
[52
]ISNI 0000 0000 9765 6057, GRID grid.266871.c, Department of Pharmacology and Neuroscience, , University of North Texas Health Science Center, ; Fort Worth, TX USA
[53
]ISNI 0000 0004 1936 9000, GRID grid.21925.3d, Departments of Psychiatry, Neurology, and Psychology, , University of Pittsburgh School of Medicine, ; Pittsburgh, PA USA
[54
]ISNI 0000000122986657, GRID grid.34477.33, National Alzheimer’s Coordinating Center, , University of Washington, ; Seattle, WA USA
[55
]ISNI 0000 0001 2299 3507, GRID grid.16753.36, Department of Pathology, , Northwestern University Feinberg School of Medicine, ; Chicago, IL USA
[56
]ISNI 0000 0001 2299 3507, GRID grid.16753.36, Cognitive Neurology and Alzheimer’s Disease Center, , Northwestern University Feinberg School of Medicine, ; Chicago, IL USA
[57
]ISNI 0000000122986657, GRID grid.34477.33, Department of Neurology, , University of Washington, ; Seattle, WA USA
[59
]ISNI 000000041936754X, GRID grid.38142.3c, Department of Epidemiology, , Harvard School of Public Health, ; Boston, MA USA
[60
]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Department of Neurology, , Mayo Clinic, ; Rochester, MN USA
[62
]ISNI 0000 0001 2297 6811, GRID grid.266102.1, Department of Neurology, , University of California San Francisco, ; San Francisco, CA USA
[63
]ISNI 0000 0004 1936 7961, GRID grid.26009.3d, Department of Medicine, , Duke University, ; Durham, NC USA
[64
]ISNI 0000 0001 2177 6375, GRID grid.412016.0, University of Kansas Alzheimer’s Disease Center, , University of Kansas Medical Center, ; Kansas City, KS USA
[65
]ISNI 0000 0001 2355 7002, GRID grid.4367.6, Department of Pathology and Immunology, , Washington University, ; St. Louis, MO USA
[66
]ISNI 0000 0001 2353 285X, GRID grid.170693.a, USF Health Byrd Alzheimer’s Institute, , University of South Florida, ; Tampa, FL USA
[67
]ISNI 0000 0001 2180 1622, GRID grid.270240.3, Fred Hutchinson Cancer Research Center, ; Seattle, WA USA
[68
]ISNI 0000 0001 2156 6853, GRID grid.42505.36, Department of Neurology, , University of Southern California, ; Los Angeles, CA USA
[69
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[70
]ISNI 0000 0001 2355 7002, GRID grid.4367.6, Department of Psychiatry and Hope Center Program on Protein Aggregation and Neurodegeneration,
, Washington University School of Medicine, ; St. Louis, MO USA
[71
]ISNI 0000 0004 1936 9684, GRID grid.27860.3b, Department of Neurology, , University of California Davis, ; Sacramento, CA USA
[72
]ISNI 0000 0001 0668 7243, GRID grid.266093.8, Institute for Memory Impairments and Neurological Disorders, , University of California Irvine, ; Irvine, CA USA
[73
]ISNI 0000 0001 2160 926X, GRID grid.39382.33, Alzheimer’s Disease and Memory Disorders Center, , Baylor College of Medicine, ; Houston, TX USA
[74
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[75
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[76
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[77
]ISNI 0000000106344187, GRID grid.265892.2, Department of Pathology, , University of Alabama at Birmingham, ; Birmingham, AL USA
[78
]ISNI 0000 0004 1936 8438, GRID grid.266539.d, Department of Biostatistics, Sanders-Brown Center on Aging, , University of Kentucky, ; Lexington, KY USA
[79
]ISNI 0000 0001 2287 3919, GRID grid.257413.6, Department of Neurology, , Indiana University, ; Indianapolis, IN USA
[80
]ISNI 0000 0004 1936 8753, GRID grid.137628.9, Department of Psychiatry, , New York University, ; New York, NY USA
[81
]ISNI 0000 0001 2107 4242, GRID grid.266100.3, Department of Neurosciences, , University of California San Diego, ; La Jolla, CA USA
[82
]ISNI 0000 0001 0941 6502, GRID grid.189967.8, Department of Pathology and Laboratory Medicine, , Emory University, ; Atlanta, GA USA
[83
]ISNI 0000 0001 0941 6502, GRID grid.189967.8, Emory Alzheimer’s Disease Center, , Emory University, ; Atlanta, GA USA
[84
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[85
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of Genetics, , Brigham and Women’s Hospital and Harvard Medical School, ; Boston, MA USA
[86
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[87
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[88
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[89
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[90
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[91
]ISNI 0000000122986657, GRID grid.34477.33, Department of Medicine (Medical Genetics), , University of Washington, ; Seattle, WA USA
[92
]ISNI 0000 0004 1936 9684, GRID grid.27860.3b, Department of Pathology and Laboratory Medicine, , University of California Davis, ; Sacramento, CA USA
[93
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[94
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[95
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[96
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[97
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[98
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[99
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[100
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[101
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[102
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[103
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[104
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[105
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[106
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[107
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[108
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[109
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[110
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[111
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[112
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[113
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[114
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[115
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[116
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[117
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[118
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[119
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[120
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[121
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[122
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Health Administration Geriatric Research Education & Clinical Center (GRECC), , UT Health Science Center at San Antonio, ; San Antonio, TX USA
[123
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[124
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, University of Cambridge, ; Cambridge, UK
[125
]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Department of Pathology, , Johns Hopkins University, ; Baltimore, MD USA
[126
]ISNI 0000 0004 1936 8438, GRID grid.266539.d, Sanders-Brown Center on Aging, Department of Anatomy and Neurobiology, , University of Kentucky, ; Lexington, KY USA
[127
]ISNI 0000 0000 9632 6718, GRID grid.19006.3e, Department of Neurology, , University of California Los Angeles, ; Los Angeles, CA USA
[128
]ISNI 0000 0000 9632 6718, GRID grid.19006.3e, Department of Pathology and Laboratory Medicine, , University of California Los Angeles, ; Los Angeles, CA USA
[129
]ISNI 0000000122483208, GRID grid.10698.36, Department of Genetics, , University of North Carolina Chapel Hill, ; Chapel Hill, NC USA
[130
]ISNI 0000 0000 9758 5690, GRID grid.5288.7, Department of Pathology, , Oregon Health and Science University, ; Portland, OR USA
Author information
Eric M. Reiman
http://orcid.org/0000-0002-0705-3696
Joseph F. Arboleda-Velasquez
http://orcid.org/0000-0002-3192-9117
Dennis W. Dickson
http://orcid.org/0000-0001-7189-7917
Bernardino F. Ghetti
http://orcid.org/0000-0002-1842-8019
Kathryn L. Lunetta
http://orcid.org/0000-0002-9268-810X
Bradley T. Hyman
http://orcid.org/0000-0002-7959-9401
Jonathan L. Haines
http://orcid.org/0000-0002-4351-4728
Margaret A. Pericak-Vance
http://orcid.org/0000-0001-7283-8804
John Q. Trojanowski
http://orcid.org/0000-0002-9239-8794
Gyungah R. Jun
http://orcid.org/0000-0002-3230-8697
Article
Publisher ID: 14279DOI: 10.1038/s41467-019-14279-8
PMC ID: 6997393
PubMed ID: 32015339
SO-VID: 4bf6f515-7213-4098-8c70-a6eb0f80bc06
Copyright © © The Author(s) 2020
License:
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
History
Date
received
: 1
October
2019
Date
accepted
: 19
December
2019
Funding
Funded by: FundRef https://doi.org/10.13039/100000049, U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S.
National Institute on Aging);
Award ID: RF1AG057519, P30-AG10161, R01AG15819, R01AG17917
Award Recipient
:
Eric M. Reiman
Categories
Subject:
Article
Custom metadata
issue-copyright-statement © The Author(s) 2020
ScienceOpen disciplines: Uncategorized