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β-Amyloid-Dependent and -Independent Genetic Pathways Regulating CSF Tau Biomarkers in Alzheimer Disease
Kumar A, Janelidze S, Stomrud E, Palmqvist S, Hansson O, Mattsson-Carlgren N, Alzheimer's Disease Neuroimaging Initiative.. Neurology, 2022-08-01
Topic: Amyloid, tau and blood-test diagnosis
Background and objectives Abnormal metabolism of β-amyloid (Aβ) and soluble phosphorylated tau (P-tau), as well as neurodegeneration, are key components of Alzheimer disease (AD), but it is unclear how these different processes are related to genetic risk factors for AD. Methods In the Swedish BioFINDER study, we tested associations between a priori defined polygenic risk scores (PRSs) for AD (excluding single-nucleotide polymorphism [SNP] within the APOE region in the main analysis) and biomarkers in CSF (total tau [T-tau] and P-tau181; Aβ1-38, Aβ1-40, Aβ1-42, and Aβ1-42/1-40; and neurofilament light [NfL]) in cognitively unimpaired (CU) individuals (n = 751), and in patients with mild cognitive impairment (MCI) (n = 212) and AD dementia (n = 150). Results were validated in the Alzheimer's Disease Neuroimaging Initiative data set with 777 individuals (AD = 119, MCI = 442, and CU = 216). Results PRSs with SNPs significant at p p = 5.6e-05) and T-tau (β = 0.12, p = 4.3e-04). The associations between PRS and tau measures were partly attenuated but remained significant after adjusting for Aβ status. Aβ pathology mediated 37% of the effect of this PRS on tau levels. Aβ-dependent and Aβ-independent subsets of the PRS were identified and characterized. There were also associations between PRSs and CSF Aβ biomarkers with nominal significance, but not when corrected for multiple comparisons. There were no associations between PRSs and CSF NfL. Discussion Genetic pathways implicated in causing AD are related to altered levels of soluble tau through both Aβ-dependent and Aβ-independent mechanisms, which may have relevance for anti-tau drug development.
Key findings
- Results were validated in the Alzheimer's Disease Neuroimaging Initiative data set with 777 individuals (AD = 119, MCI = 442, and CU = 216).
- Results PRSs with SNPs significant at p p = 5.6e-05) and T-tau (β = 0.12, p = 4.3e-04).
- The associations between PRS and tau measures were partly attenuated but remained significant after adjusting for Aβ status.
Why it matters
In the BioFINDER and ADNI cohorts, polygenic risk scores for Alzheimer's disease were associated with CSF tau biomarkers, partly through amyloid pathology and partly independently of it. This is about genetic contributions to tau biomarker levels, not about treating, curing or preventing Alzheimer's disease.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Participants751
- Evidence strengthLow
How this study scored 48/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 46 of the 96 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 751 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 16 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.7 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 2 / 6 | Cited 1.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 1 / 4 | Cited 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 1 / 3 | Lund University: institution h-index 1,119 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35641311) |
| Free to read | 2 / 2 | Free to read |
| Points | 46 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 46 of the 96 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Kumar, A., Janelidze, S., Stomrud, E., Palmqvist, S., Hansson, O., Mattsson-Carlgren, N., et al. (2022). β-Amyloid-Dependent and -Independent Genetic Pathways Regulating CSF Tau Biomarkers in Alzheimer Disease. Neurology. https://doi.org/10.1212/wnl.0000000000200605
Vancouver
Kumar A, Janelidze S, Stomrud E, Palmqvist S, Hansson O, Mattsson-Carlgren N, et al. β-Amyloid-Dependent and -Independent Genetic Pathways Regulating CSF Tau Biomarkers in Alzheimer Disease. Neurology. 2022. doi:10.1212/wnl.0000000000200605. PMID: 35641311.
BibTeX
@article{kumar2022-35641311,
author = {Kumar, A. and Janelidze, S. and Stomrud, E. and Palmqvist, S. and Hansson, O. and Mattsson-Carlgren, N. and {Alzheimer's Disease Neuroimaging Initiative}},
title = {{β-Amyloid-Dependent and -Independent Genetic Pathways Regulating CSF Tau Biomarkers in Alzheimer Disease}},
journal = {Neurology},
year = {2022},
doi = {10.1212/wnl.0000000000200605},
pmid = {35641311},
url = {https://doi.org/10.1212/wnl.0000000000200605}
}
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