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APOEε4 potentiates the relationship between amyloid-β and tau pathologies
Joseph Therriault, Andrea L Benedet, Tharick A Pascoal, Sulantha Mathotaarachchi, Melissa Savard, Mira Chamoun, Emilie Thomas, Min Su Kang et al.. Molecular psychiatry, 2020-03-11
Topic: Genetics and APOE
APOEε4 is the most well-established genetic risk factor for sporadic Alzheimer's disease and is associated with cerebral amyloid-β. However, the association between APOEε4 and tau pathology, the other major proteinopathy of Alzheimer's disease, has been controversial. Here, we sought to determine whether the relationship between APOEε4 and tau pathology is determined by local interactions with amyloid-β. We examined three independent samples of cognitively unimpaired, mild cognitive impairment and Alzheimer's disease subjects: (1) 211 participants who underwent tau-PET with [18F]MK6240 and amyloid-PET with [18F]AZD4694, (2) 264 individuals who underwent tau-PET with [18F]Flortaucipir and amyloid-PET with [18F]Florbetapir and (3) 487 individuals who underwent lumbar puncture and amyloid-PET with [18F]Florbetapir. Using a novel analytical framework, we applied voxel-wise regression models to assess the interactive effect of APOEε4 and amyloid-β on tau load, independently of age and clinical diagnosis. We found that the interaction effect between APOEε4 and amyloid-β, rather than the sum of their independent effects, was related to increased tau load in Alzheimer's disease-vulnerable regions. The interaction between one APOEε4 allele and amyloid-β was related to increased tau load, while the interaction between amyloid-β and two APOEε4 alleles was related to a more widespread pattern of tau aggregation. Our results contribute to an emerging framework in which the elevated risk of developing dementia conferred by APOEε4 genotype involves mechanisms associated with both amyloid-β and tau aggregation. These results may have implications for future disease-modifying therapeutic trials targeting amyloid or tau pathologies.
Key findings
- APOEε4 is the most well-established genetic risk factor for sporadic Alzheimer's disease and is associated with cerebral amyloid-β.
- We found that the interaction effect between APOEε4 and amyloid-β, rather than the sum of their independent effects, was related to increased tau load in Alzheimer's disease-vulnerable regions.
- Our results contribute to an emerging framework in which the elevated risk of developing dementia conferred by APOEε4 genotype involves mechanisms associated with both amyloid-β and tau aggregation.
- These results may have implications for future disease-modifying therapeutic trials targeting amyloid or tau pathologies.
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Study details
- Participants211
- Evidence strengthLow
How this study scored 54/100
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 journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 30 of the 56 points we could judge it on, which is 54 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 211 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32161362) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 30 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 30 of the 56 points we could judge it on is 54 out of 100. |
| Total | 54 / 100 | — |
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Read the original
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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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Therriault, J., Benedet, A. L., Pascoal, T. A., Mathotaarachchi, S., Savard, M., Chamoun, M., et al. (2021). APOEε4 potentiates the relationship between amyloid-β and tau pathologies. Molecular psychiatry. https://doi.org/10.1038/s41380-020-0688-6
Vancouver
Therriault J, Benedet AL, Pascoal TA, Mathotaarachchi S, Savard M, Chamoun M, et al. APOEε4 potentiates the relationship between amyloid-β and tau pathologies. Molecular psychiatry. 2021. doi:10.1038/s41380-020-0688-6. PMID: 32161362.
BibTeX
@article{therriault2021-32161362,
author = {Therriault, Joseph and Benedet, Andrea L and Pascoal, Tharick A and Mathotaarachchi, Sulantha and Savard, Melissa and Chamoun, Mira and Thomas, Emilie and Kang, Min Su and others},
title = {{APOEε4 potentiates the relationship between amyloid-β and tau pathologies}},
journal = {Molecular psychiatry},
year = {2021},
doi = {10.1038/s41380-020-0688-6},
pmid = {32161362},
url = {https://doi.org/10.1038/s41380-020-0688-6}
}
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