| Title: | Alzheimer's Disease Susceptibility Gene Apolipoprotein E (APOE) and Blood Biomarkers in UK Biobank (N = 395,769). |
| Journal: | Journal of Alzheimer's Disease |
| Published: | 1 Jan 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32651323/ |
| DOI: | https://doi.org/10.3233/jad-200338 |
| URL: | https://eprints.gla.ac.uk/217500/1/217500.pdf |
| Citations: | 14 (5 in last 2 years) as of 8 Aug 2024 |
Publication 3403
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Abstract
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative condition where the underlying etiology is still unclear. Investigating the potential influence of apolipoprotein E (APOE), a major genetic risk factor, on common blood biomarkers could provide a greater understanding of the mechanisms of AD and dementia risk.</p>
OBJECTIVE: Our objective was to conduct the largest (to date) single-protocol investigation of blood biomarkers in the context of APOE genotype, in UK Biobank.</p>
METHODS: After quality control and exclusions, data on 395,769 participants of White European ancestry were available for analysis. Linear regressions were used to test potential associations between APOE genotypes and biomarkers.</p>
RESULTS: Several biomarkers significantly associated with APOEɛ4 'risk' and ɛ2 'protective' genotypes (versus neutral ɛ3/ɛ3). Most associations supported previous data: for example, ɛ4 genotype was associated with elevated low-density lipoprotein cholesterol (LDL) (standardized beta [b] = 0.150 standard deviations [SDs] per allele, p < 0.001) and ɛ2 with lower LDL (b = -0.456 SDs, p < 0.001). There were however instances of associations found in unexpected directions: e.g., ɛ4 and increased insulin-like growth factor (IGF-1) (b = 0.017, p < 0.001) where lower levels have been previously suggested as an AD risk factor.</p>
CONCLUSION: These findings highlight biomarker differences in non-demented people at genetic risk for dementia. The evidence herein supports previous hypotheses of involvement from cardiometabolic and neuroinflammatory pathways.</p>
14 Keywords
- Adult
- Aged
- Alzheimer Disease
- Apolipoproteins E
- Biological Specimen Banks
- Cholesterol
- Disease Susceptibility
- Female
- Genetic Predisposition to Disease
- Genotype
- Humans
- Male
- Middle Aged
- United Kingdom
18 Authors
- Amy C Ferguson
- Rachana Tank
- Laura M Lyall
- Joey Ward
- Carlos Celis-Morales
- Rona Strawbridge
- Frederick Ho
- Christopher D Whelan
- Jason Gill
- Paul Welsh
- Jana J Anderson
- Patrick B Mark
- Daniel F Mackay
- Daniel J Smith
- Jill P Pell
- Jonathan Cavanagh
- Naveed Sattar
- Donald M Lyall
1 Application
| Application ID | Title |
|---|---|
| 17689 | Genetic, environmental and lifestyle predictors of brain/cognitive-related outcomes. |
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