Skoog, I;
Kern, S;
Najar, J;
Guerreiro, R;
Bras, J;
Waern, M;
Zetterberg, H;
... Zettergren, A; + view all
(2021)
A non-APOE polygenic risk score for Alzheimer's disease is associated with CSF neurofilament light in a representative sample of cognitively unimpaired 70-year-olds.
The Journals of Gerontology: Series A
10.1093/gerona/glab030.
(In press).
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Abstract
The effect of Alzheimer's disease (AD) polygenic risk scores (PRSs) on amyloid and tau pathophysiology and neurodegeneration in cognitively unimpaired older adults is not known in detail. This study aims to investigate non-APOE AD-PRS and APOE ε4 in relation to AD pathophysiology evaluated by cerebrospinal fluid (CSF) biomarkers in a population-based sample of 70-year-olds. A total of 303 dementia-free individuals from the Gothenburg H70 Birth Cohort Studies were included. Genotyping was performed using the NeuroChip, and AD-PRSs were calculated. CSF levels of amyloid-β (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), neurogranin (Ng), and neurofilament light (NfL) were measured with ELISA. Associations were found between non-APOE PRS and both NfL (p=0.001) and Aβ42 (p=0.02), and between APOE ε4 and Aβ42 (p=1e-10), t-tau (p=5e-4), and p-tau (p=0.002). Similar results were observed when only including individuals with CDR=0, except for no evidence of an association between non-APOE PRS and Aβ42. There was an interaction between non-APOE PRS and Aβ42 pathology status in relation to NfL (p=0.005); association was only present in individuals without Aβ42 pathology (p=0.0003). In relation to Aβ42, there was a borderline interaction (p=0.06) between non-APOE PRS and APOE ε4; association was present in ε4 carriers only (p=0.03). Similar results were observed in individuals with CDR=0 (n=246). In conclusion, among cognitively healthy 70-year-olds from the general population genetic risk of AD beyond the APOE locus was associated with NfL in individuals without Aβ42 pathology, and with Aβ42 in APOE ε4 carriers, suggesting these associations are driven by different mechanisms.
| Type: | Article |
|---|---|
| Title: | A non-APOE polygenic risk score for Alzheimer's disease is associated with CSF neurofilament light in a representative sample of cognitively unimpaired 70-year-olds |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/gerona/glab030 |
| Publisher version: | https://doi.org/10.1093/gerona/glab030 |
| Language: | English |
| Additional information: | This is an Open Access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits noncommercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
| Keywords: | CSF biomarkers, amyloid-beta, genetic variants, tau |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10121824 |
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