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Cited by 73Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchGenetic Associations and Epidemiology

Genome-wide association study of brain amyloid deposition as measured by Pittsburgh Compound-B (PiB)-PET imaging

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for the Alzheimer’s Disease Neuroimaging Initiative (ADNI), Yan, Qi, Nho, Kwangsik, Del-Aguila, Jorge L., Wang, Xingbin, Risacher, Shannon L., Fan, Kang-Hsien, Snitz, Beth E. +9 more·2021·Molecular Psychiatry
DOI 10.1038/s41380-018-0246-7PMC PMC6219464
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Abstract

Deposition of amyloid plaques in the brain is one of the two main pathological hallmarks of Alzheimer’s disease (AD). Amyloid positron emission tomography (PET) is a neuroimaging tool that selectively detects in vivo amyloid deposition in the brain and is a reliable endophenotype for AD that complements cerebrospinal fluid biomarkers with regional information. We measured in vivo amyloid deposition in the brains of ~1000 subjects from three collaborative AD centers and ADNI using 11 C-labeled Pittsburgh Compound-B (PiB)-PET imaging followed by meta-analysis of genome-wide association studies, first to our knowledge for PiB-PET, to identify novel genetic loci for this endophenotype. The APOE region showed the most significant association where several SNPs surpassed the genome-wide significant threshold, with APOE*4 being most significant (P-meta = 9.09E-30; β = 0.18). Interestingly, after conditioning on APOE*4, 14 SNPs remained significant at P < 0.05 in the APOE region that were not in linkage disequilibrium with APOE*4. Outside the APOE region, the meta-analysis revealed 15 non-APOE loci with P < 1E-05 on nine chromosomes, with two most significant SNPs on chromosomes 8 (P-meta = 4.87E-07) and 3 (P-meta = 9.69E-07). Functional analyses of these SNPs indicate their potential relevance with AD pathogenesis. Top 15 non-APOE SNPs along with APOE*4 explained 25–35% of the amyloid variance in different datasets, of which 14–17% was explained by APOE*4 alone. In conclusion, we have identified novel signals in APOE and non-APOE regions that affect amyloid deposition in the brain. Our data also highlights the presence of yet to be discovered variants that may be responsible for the unexplained genetic variance of amyloid deposition.

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  • Only 5 of the 12 SNPs in the APOE region were present in the amyloid-PET GWAS data, and all 5 were associated with amyloid deposition.

    “Only 5 of the 12 SNPs in the APOE region were present in the amyloid-PET GWAS data [25] and all 5 were also associated with amyloid deposition.”

    From Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer’s disease risk (2023) · cites this paper as [25]

    The Results section (‘Conditional analysis in the APOE region’; page unavailable) reports APOE-region SNPs associated with PiB retention, supporting the general association with amyloid deposition. It does not identify the citing paper’s set of 12 SNPs or establish that exactly five of them were present in this GWAS, so the specific five-of-twelve claim is not supported by our copy. (LLM, conf=0.82)

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Cited by

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Authors
(ADNI), F. T. A. D. N. I., Yan, Q., Nho, K., Del-Aguila, J. L., Wang, X., Risacher, S. L., Fan, K.-H., Snitz, B. E., Aizenstein, H. J., Mathis, C. A., Lopez, O. L., Demirci, F. Y., Feingold, E., Klunk, W. E., Saykin, A. J., Cruchaga, C., & Kamboh, M. I.
Affiliations
  • University of Pittsburgh (US)
  • Washington University in St. Louis (US)
Corresponding author
Kamboh, M. Ilyas
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2018-10-25
Volume
26
Issue
1
Pages
309-321
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/s41380-018-0246-7
PMC
PMC6219464
OpenAlex
W2898262363
Cited by
73
References
12
Citations by year
2026: 8 · 2025: 9 · 2024: 11 · 2023: 15 · 2022: 13 · 2021: 6 · 2020: 7 · 2019: 3 · 2018: 1
FWCI
2.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
  • IUScholarWorks (Indiana University) (submittedVersion)
  • PMC
Funders
  • U.S. Department of Defense (W81XWH, W81XWH-12-2-, W81XWH-12, W81XWH1220012, AG024904)
  • National Institutes of Health (5u01ag024904-10, W81XWH, W81XWH-12-2-0012, AG005133, AG05681, AG024904, AG025204, AG003991, AG025516)
  • National Institute on Aging (U01-AG-024904, R01AG064877, RF1AG044546, R01AG052521, P01AG025204, R01AG041718, RF1AG025516, P50AG005133, RF1AG053303, R01AG030653, R01AG044546, P50AG005681, P01AG003991, R37AG025516, R03AG054936, P30AG066468, P30AG066444, U19AG024904, P01AG026276, U24AG021886, R01AG072641, R01AG025516)
  • U.S. National Library of Medicine (R01LM012535)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
brain amyloid deposition, Pittsburgh compound B PET, Alzheimer's disease, APOE ε4, apolipoprotein E, genetic loci, single nucleotide polymorphisms, genetic susceptibility, amyloid plaques, endophenotypes, chromosome 8, chromosome 3
MeSH terms
Alzheimer Disease, Aniline Compounds, Brain, Female, Humans, Male, Thiazoles, Amyloid beta-Peptides, Polymorphism, Single Nucleotide, Positron-Emission Tomography, Apolipoprotein E4, Genome-Wide Association Study, Endophenotypes

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