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Home › Research › Disease mechanisms

APOE4 exacerbates α-synuclein pathology and related toxicity independent of amyloid

Zhao N, Attrebi ON, Ren Y, Qiao W, Sonustun B, Martens YA, Meneses AD, Li F et al.. Science translational medicine, 2020-02-01

This page is alzhub.org's plain-English summary of a published study, not the paper itself. It is generated from the record we hold for this study, sourced and linked below — check the original for the full text and methods.

✓ Peer-reviewed alzhub usefulness score 38 out of 100. Disease mechanisms

Topic: Brain proteins, microglia and lab models

The apolipoprotein E ( APOE ) ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease mainly by driving amyloid-β pathology. Recently, APOE4 has also been found to be a genetic risk factor for Lewy body dementia (LBD), which includes dementia with Lewy bodies and Parkinson's disease dementia. How APOE4 drives risk of LBD and whether it has a direct effect on α-synuclein pathology are not clear. Here, we generated a mouse model of synucleinopathy using an adeno-associated virus gene delivery of α-synuclein in human APOE-targeted replacement mice expressing APOE2, APOE3, or APOE4. We found that APOE4, but not APOE2 or APOE3, increased α-synuclein pathology, impaired behavioral performances, worsened neuronal and synaptic loss, and increased astrogliosis at 9 months of age. Transcriptomic profiling in APOE4-expressing α-synuclein mice highlighted altered lipid and energy metabolism and synapse-related pathways. We also observed an effect of APOE4 on α-synuclein pathology in human postmortem brains with LBD and minimal amyloid pathology. Our data demonstrate a pathogenic role of APOE4 in exacerbating α-synuclein pathology independent of amyloid, providing mechanistic insights into how APOE4 increases the risk of LBD.

Key findings

Study details

How this study scored 38/100
How this study's score is builtJournal tier 7 of 10; Journal's citation record left out, no data; Study design 0 of 12; Strength of evidence 1 of 5; Peer-review validation 10 of 10; How recent 2 of 5; Sample size 0 of 4; Effect reported 0 of 3; Studied in people 0 of 3; Randomised / blinded 0 of 2; Times cited left out, no data; Citations per year left out, no data; Impact for its field and year left out, no data; Cited by studies here left out, no data; Still being cited left out, no data; Senior author's track record left out, no data; Institution's track record left out, no data; Multi-centre collaboration left out, no data; Indexed in PubMed 2 of 2; Free to read 0 of 2. 22 of the 58 points it could be judged on, which is 38 of 100. Total 38 of 100.22 of the 58 points we could judge = 38 of 100

Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people 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 and multi-centre collaboration, so those were left out: it earned 22 of the 58 points we could judge it on, which is 38 out of 100.

ComponentPointsWhy
Journal tier 7 / 10 Tier 3 — peer-reviewed journal (Science translational medicine)
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 2 / 5 2020 — within 10 year(s) of the newest study here
Sample size 0 / 4 Participant count not stated — scores zero (not stated in the record — scored 0)
Effect reported 0 / 3 No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people 0 / 3 Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
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 32024798)
Free to read 0 / 2 Behind a paywall — scores zero
Points 22 / 58 Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 22 of the 58 points we could judge it on is 38 out of 100.
Total 38 / 100 —

What each of these 20 components measures, and what this score is not →

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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

Zhao, N., Attrebi, O. N., Ren, Y., Qiao, W., Sonustun, B., Martens, Y. A., et al. (2020). APOE4 exacerbates α-synuclein pathology and related toxicity independent of amyloid. Science translational medicine. https://doi.org/10.1126/scitranslmed.aay1809

Vancouver

Zhao N, Attrebi ON, Ren Y, Qiao W, Sonustun B, Martens YA, et al. APOE4 exacerbates α-synuclein pathology and related toxicity independent of amyloid. Science translational medicine. 2020. doi:10.1126/scitranslmed.aay1809. PMID: 32024798.

BibTeX

@article{zhao2020-32024798,
  author  = {Zhao, N. and Attrebi, O. N. and Ren, Y. and Qiao, W. and Sonustun, B. and Martens, Y. A. and Meneses, A. D. and Li, F. and others},
  title   = {{APOE4 exacerbates α-synuclein pathology and related toxicity independent of amyloid}},
  journal = {Science translational medicine},
  year    = {2020},
  doi     = {10.1126/scitranslmed.aay1809},
  pmid    = {32024798},
  url     = {https://doi.org/10.1126/scitranslmed.aay1809}
}

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