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Cited by 67Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsGenetic Associations and Epidemiology

Genome‐wide association study of Alzheimer's disease endophenotypes at prediagnosis stages

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Chung, Jaeyoon, Wang, Xulong, Maruyama, Toru, Ma, Yiyi, Zhang, Xiaoling, Mez, Jesse, Sherva, Richard, Takeyama, Haruko +4 more·2018·Alzheimer's & Dementia
DOI 10.1016/j.jalz.2017.11.006PMC PMC5938137
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Abstract

Introduction: Genetic associations for endophenotypes of Alzheimer's disease (AD) in cognitive stages preceding AD have not been thoroughly evaluated. Methods: We conducted genome‐wide association studies for AD‐related endophenotypes including hippocampal volume, logical memory scores, and cerebrospinal fluid Aβ 42 and total/phosphorylated tau in cognitively normal (CN), mild cognitive impairment, and AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative study. Results: In CN subjects, study‐wide significant (P < 8.3 × 10−9) loci were identified for total tau near SRRM4 and C14orf79 and for hippocampal volume near MTUS1. In mild cognitive impairment subjects, study‐wide significant association was found with single nucleotide polymorphisms (SNPs) near ZNF804B for logical memory test of delayed recall scores. We found consistent expression patterns of C14orf40 and MTUS1 in carriers with risk alleles of expression SNPs and in brains of AD patients, compared with in the noncarriers and in brains of controls. Discussion: Our findings for AD‐related brain changes before AD provide insight about early AD‐related biological processes.

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  • APOE genotype was associated with lower Aβ42 and higher T-tau and P-tau in CSF, validating known associations with Alzheimer's disease biomarkers.

    “This genetic variant defines the APOE genotype, which has well‐known associations with CSF biomarkers related to Alzheimer's disease (AD), which were validated here (lower Aβ42, higher T‐tau and P‐tau (Chung et al, 2018)).”

    From The genetic regulation of protein expression in cerebrospinal fluid (2023) · cites this paper as Chung et al, 2018

    The Results (§3.1) and Discussion (§4; page unavailable) report APOE ε4 associations with CSF Aβ42, total tau, and phosphorylated tau in people with mild cognitive impairment. They do not state the claimed directions—lower Aβ42 and higher tau—and the Discussion says APOE ε4 was not associated with CSF tau biomarkers in cognitively normal subjects. (LLM, conf=0.86)

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Authors
Chung, J., Wang, X., Maruyama, T., Ma, Y., Zhang, X., Mez, J., Sherva, R., Takeyama, H., Initiative, T. A. D. N., Lunetta, K. L., Farrer, L. A., & Jun, G. R.
Affiliations
  • Boston University (US)
  • Eisai (United States) (US)
  • Waseda University (JP)
Corresponding author
Jun, Gyungah R.
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2017-12-20
Volume
14
Issue
5
Pages
623-633
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1016/j.jalz.2017.11.006
PMC
PMC5938137
OpenAlex
W2775900076
Cited by
67
References
9
Citations by year
2026: 3 · 2025: 5 · 2024: 7 · 2023: 12 · 2022: 6 · 2021: 10 · 2020: 9 · 2019: 7 · 2018: 8
FWCI
5.22
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Alzheimer s & Dementia (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (RF1‐AG057519, R01‐AG048927, U01‐AG032984, UF1‐AG046198, P30‐AG13846)
  • Alzheimer's Disease Neuroimaging Initiative
  • National Institute on Aging (U01 AG024904)
  • National Institute of Biomedical Imaging and Bioengineering
  • Northern California Institute for Research and Education
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
Alzheimer's disease, endophenotypes
MeSH terms
Alzheimer Disease, Female, Humans, Magnetic Resonance Imaging, Male, Nerve Tissue Proteins, Phosphorylation, Biomarkers, Amyloid beta-Peptides, tau Proteins, Polymorphism, Single Nucleotide, Early Diagnosis, Genome-Wide Association Study, Endophenotypes, Cognitive Dysfunction

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