Evidence that PICALM affects age at onset of Alzheimer's dementia in Down syndrome
Open accessAbstract
It is known that individuals with Down syndrome develop Alzheimer's disease with an early age at onset, although associated genetic risk factors have not been widely studied. We tested whether genes that increase the risk of late-onset Alzheimer's disease influence the age at onset in Down syndrome using genome-wide association data for age at onset of dementia in a small sample of individuals (N = 67) with Down syndrome. We tested for association with loci previously associated with Alzheimer's disease risk and, despite the small size of the study, we detected associations with age at onset of Alzheimer's disease in Down syndrome with PICALM (β = 3.31, p = 0.011) and the APOE loci (β = 3.58, p = 0.014). As dementia in people with Down syndrome is relatively understudied, we make all of these data publicly available to encourage further analyses of the problem of Alzheimer's disease in Down syndrome.
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APOE remains the only locus repeatedly associated with AAO, but PICALM and BIN1 have also been reported to affect AAO.
“To date, APOE remains the only locus repeatedly associated with AAO8,9, but PICALM and BIN1 have also been reported to affect AAO6,10,11.”
From A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease (2017) · cites this paper as [11]
The Results (page unavailable) report an association between PICALM variants and age at onset of Alzheimer’s dementia in people with Down syndrome. The Introduction lists BIN1 as an Alzheimer’s disease risk gene, but the paper does not report a BIN1 association with age at onset. The APOE clause has separate citations and is not attributed to this source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe association of PICALM polymorphisms with late-onset AD has been reported by the majority of GWAS studies.
“The association of PICALM polymorphisms with late-onset AD has been reported by the majority of GWAS studies (94, 119, 236, 265, 298, 344, 528).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [298]
The Introduction reports that large GWAS identified PICALM as an Alzheimer’s disease risk gene, and the Discussion describes PICALM variants associated with AD risk in the general population. Neither passage establishes that a majority of GWAS studies reported the association. (LLM, conf=0.84)
Experimental — accuracy not yet measured
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PICALM and Alzheimer’s Disease: An Update and Perspectives
Ando, K., Nagaraj, S., Küçükali, F., de Fisenne, M.-A., Kosa, A.-C., Doeraene, E., Lopez Gutierrez, L., Brion, J.-P., & Leroy, K. (2022) · Cells · doi:10.3390/cells11243994 · Cited by 104 · see citing works
- Authors
- Jones, E. L., Mok, K., Hanney, M., Harold, D., Sims, R., Williams, J., & Ballard, C.
- Affiliations
- King's College London (GB)
- National Hospital for Neurology and Neurosurgery (GB)
- Cardiff University (GB)
- Corresponding author
- Jones, Emma L.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 34
- Issue
- 10
- Pages
- 2441.e1-2441.e5
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC3898582
- OpenAlex
- W2011503072
- Cited by
- 47
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 9 · 2013: 1
- FWCI
- 6.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurobiology of Aging (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute for Health Research
- Maudsley NHS Foundation Trust
- King's College London
- Alzheimer’s Society
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Down syndrome, Alzheimer's disease, PICALM, apolipoprotein E, genetic risk factors, genome-wide association study
- MeSH terms
- Adult, Aged, Alleles, Alzheimer Disease, Apolipoproteins E, Down Syndrome, Female, Humans, Male, Middle Aged, Risk, Age of Onset, Sample Size, Polymorphism, Single Nucleotide, Monomeric Clathrin Assembly Proteins, Genome-Wide Association Study
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