Effect of ApoE isoforms on mitochondria in Alzheimer disease
Yin J, Reiman EM, Beach TG, Serrano GE, Sabbagh MN, Nielsen M, Caselli RJ, Shi J.. Neurology, 2020-05-26
Topic: Amyloid, tau and blood-test diagnosis
Objective To test the hypothesis that ApoE isoforms affect mitochondrial structure and function that are related to cognitive impairment in Alzheimer disease (AD), we systematically investigated the effects of ApoE isoforms on mitochondrial biogenesis and dynamics, oxidative stress, synapses, and cognitive performance in AD. Methods We obtained postmortem human brain tissues and measured proteins that are responsible for mitochondrial biogenesis (peroxisome proliferator-activated receptor-gamma coactivator-1α [PGC-1α] and sirtuin 3 [SIRT3]), for mitochondrial dynamics (mitofusin 1 [MFN1], mitofusin 2 [MFN2], and dynamin-like protein 1 [DLP1]), for oxidative stress (superoxide dismutase 2 [SOD2] and forkhead-box protein O3a [Foxo3a]), and for synapses (postsynaptic density protein 95 [PSD95] and synapsin1 [Syn1]). A total of 46 cases were enrolled, including ApoE-ɛ4 carriers (n = 21) and noncarriers (n = 25). Results Levels of these proteins were compared between ApoE-ɛ4 carriers and noncarriers. ApoE-ɛ4 was associated with impaired mitochondrial structure and function, oxidative stress, and synaptic integrity in the human brain. Correlation analysis revealed that mitochondrial proteins and the synaptic protein were strongly associated with cognitive performance. Conclusion ApoE isoforms influence mitochondrial structure and function, which likely leads to alteration in oxidative stress, synapses, and cognitive function. These mitochondria-related proteins may be a harbinger of cognitive decline in ApoE-ɛ4 carriers and provide novel therapeutic targets for prevention and treatment of AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Yin, J., Reiman, E. M., Beach, T. G., Serrano, G. E., Sabbagh, M. N., Nielsen, M., et al. (2020). Effect of ApoE isoforms on mitochondria in Alzheimer disease. Neurology. https://doi.org/10.1212/wnl.0000000000009582
Vancouver
Yin J, Reiman EM, Beach TG, Serrano GE, Sabbagh MN, Nielsen M, et al. Effect of ApoE isoforms on mitochondria in Alzheimer disease. Neurology. 2020. doi:10.1212/wnl.0000000000009582. PMID: 32457210.
BibTeX
@article{yin2020-32457210,
author = {Yin, J. and Reiman, E. M. and Beach, T. G. and Serrano, G. E. and Sabbagh, M. N. and Nielsen, M. and Caselli, R. J. and Shi, J.},
title = {{Effect of ApoE isoforms on mitochondria in Alzheimer disease}},
journal = {Neurology},
year = {2020},
doi = {10.1212/wnl.0000000000009582},
pmid = {32457210},
url = {https://doi.org/10.1212/wnl.0000000000009582}
}
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Key findings
- Results Levels of these proteins were compared between ApoE-ɛ4 carriers and noncarriers.
- ApoE-ɛ4 was associated with impaired mitochondrial structure and function, oxidative stress, and synaptic integrity in the human brain.
- Correlation analysis revealed that mitochondrial proteins and the synaptic protein were strongly associated with cognitive performance.
Why it matters
In postmortem brain tissue from 46 cases, ApoE-ε4 carriers showed impaired mitochondrial structure and function, oxidative stress, and synaptic damage compared to noncarriers. These mitochondrial and synaptic proteins were strongly associated with cognitive performance, but the study is observational and does not test any intervention.
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Study details
- Participants21
- Evidence strengthLow
How this study scored 54/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it.
| 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 | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 1 / 4 | 21 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 117 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.6 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 4 / 6 | Cited 8.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 3 / 4 | Cited 53 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Jiong Shi: h-index 34 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Cleveland Clinic: institution h-index 1,139 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32457210) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 54 / 100 | — |
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Read the original
- DOI: 10.1212/wnl.0000000000009582
- PubMed: 32457210
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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