Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of β-amyloidosis
Huynh TV, Liao F, Francis CM, Robinson GO, Serrano JR, Jiang H, Roh J, Finn MB et al.. Neuron, 2017-12-01
Topic: Brain proteins, microglia and lab models
The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer disease. Previous studies suggest that reduction of apoE levels through genetic manipulation can reduce Aβ pathology. However, it is not clear how reduction of apoE levels after birth would affect amyloid deposition. We utilize an antisense oligonucleotide (ASO) to reduce apoE expression in the brains of APP/PS1-21 mice homozygous for the APOE-ε4 or APOE-ε3 allele. ASO treatment starting after birth led to a significant decrease in Aβ pathology when assessed at 4 months. Interestingly, ASO treatment starting at the onset of amyloid deposition led to an increase in Aβ plaque size and a reduction in plaque-associated neuritic dystrophy with no change in overall plaque load. These results suggest that lowering apoE levels prior to plaque deposition can strongly affect the initiation of Aβ pathology while lowering apoE after Aβ seeding modulates plaque size and toxicity.
Key findings
- Previous studies suggest that reduction of apoE levels through genetic manipulation can reduce Aβ pathology.
- ASO treatment starting after birth led to a significant decrease in Aβ pathology when assessed at 4 months.
- Interestingly, ASO treatment starting at the onset of amyloid deposition led to an increase in Aβ plaque size and a reduction in plaque-associated neuritic dystrophy with no change in overall plaque load.
- These results suggest that lowering apoE levels prior to plaque deposition can strongly affect the initiation of Aβ pathology while lowering apoE after Aβ seeding modulates plaque size and toxicity.
Why it matters
In APP/PS1-21 mice, reducing apoE with an antisense oligonucleotide before plaque deposition decreased amyloid pathology, while starting treatment at the onset of amyloid deposition increased plaque size and reduced plaque-associated neuritic dystrophy without changing overall plaque load. These are mouse results showing that timing of apoE reduction matters, and they do not establish a treatment for people.
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Study details
- Evidence strengthLow
How this study scored 52/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuron) |
| Journal's citation record | 4 / 4 | Neuron: journal h-index 689 (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 | 2017 — 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 | 5 / 7 | Cited 210 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 19.1 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 4 / 6 | Cited 9.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 22 other studies in this library |
| Still being cited | 3 / 4 | Cited 74 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author David M. Holtzman: h-index 206 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29216448) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
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Read the original
- DOI: 10.1016/j.neuron.2017.11.014
- PubMed: 29216448
- 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).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Huynh, T. V., Liao, F., Francis, C. M., Robinson, G. O., Serrano, JR., Jiang, H., et al. (2017). Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of β-amyloidosis. Neuron. https://doi.org/10.1016/j.neuron.2017.11.014
Vancouver
Huynh TV, Liao F, Francis CM, Robinson GO, Serrano JR, Jiang H, et al. Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of β-amyloidosis. Neuron. 2017. doi:10.1016/j.neuron.2017.11.014. PMID: 29216448.
BibTeX
@article{huynh2017-29216448,
author = {Huynh, T. V. and Liao, F. and Francis, C. M. and Robinson, G. O. and Serrano, JR. and Jiang, H. and Roh, J. and Finn, M. B. and others},
title = {{Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of β-amyloidosis}},
journal = {Neuron},
year = {2017},
doi = {10.1016/j.neuron.2017.11.014},
pmid = {29216448},
url = {https://doi.org/10.1016/j.neuron.2017.11.014}
}
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