ApoE4 decreases spine density and dendritic complexity in cortical neurons in vivo
Sonya B Dumanis, Joseph A Tesoriero, Lenard W Babus, Madeline T Nguyen, Justin H Trotter, Mary Jo Ladu, Edwin J Weeber, R Scott Turner et al.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009-12-02
Topic: Genetics and APOE
The three human alleles of apolipoprotein E (APOE) differentially influence outcome after CNS injury and affect one's risk of developing Alzheimer's disease (AD). It remains unclear how ApoE isoforms contribute to various AD-related pathological changes (e.g., amyloid plaques and synaptic and neuron loss). Here, we systematically examined whether apoE isoforms (E2, E3, E4) exhibit differential effects on dendritic spine density and morphology in APOE targeted replacement (TR) mice, which lack AD pathological changes. Using Golgi staining, we found age-dependent effects of APOE4 on spine density in the cortex. The APOE4 TR mice had significantly reduced spine density at three independent time points (4 weeks, 3 months, and 1 year, 27.7% +/- 7.4%, 24.4% +/- 8.6%, and 55.6% +/- 10.5%, respectively) compared with APOE3 TR mice and APOE2 TR mice. Additionally, in APOE4 TR mice, shorter spines were evident compared with other APOE TR mice at 1 year. APOE2 TR mice exhibited longer spines as well as significantly increased apical dendritic arborization in the cortex compared with APOE4 and APOE3 TR mice at 4 weeks. However, there were no differences in spine density across APOE genotypes in hippocampus. These findings demonstrate that apoE isoforms differentially affect dendritic complexity and spine formation, suggesting a role for APOE genotypes not only in acute and chronic brain injuries including AD, but also in normal brain functions.
Key findings
- Using Golgi staining, we found age-dependent effects of APOE4 on spine density in the cortex.
- The APOE4 TR mice had significantly reduced spine density at three independent time points (4 weeks, 3 months, and 1 year, 27.7% +/- 7.4%, 24.4% +/- 8.6%, and 55.6% +/- 10.5%, respectively) compared with APOE3 TR mice and APOE2 TR mice.
- Additionally, in APOE4 TR mice, shorter spines were evident compared with other APOE TR mice at 1 year.
- APOE2 TR mice exhibited longer spines as well as significantly increased apical dendritic arborization in the cortex compared with APOE4 and APOE3 TR mice at 4 weeks.
- These findings demonstrate that apoE isoforms differentially affect dendritic complexity and spine formation, suggesting a role for APOE genotypes not only in acute and chronic brain injuries including AD, but also in normal brain functions.
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Study details
- Effect size27.7%; 7.4%; 24.4%
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, 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, multi-centre collaboration and free to read, so those were left out: it earned 23 of the 56 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of neuroscience : the official journal of the Society for Neuroscience) |
| 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 | 1 / 5 | 2009 — within 20 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 19955384) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 23 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 23 of the 56 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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APA 7th
Dumanis, S. B., Tesoriero, J. A., Babus, L. W., Nguyen, M. T., Trotter, J. H., Ladu, M. J., et al. (2009). ApoE4 decreases spine density and dendritic complexity in cortical neurons in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.4026-09.2009
Vancouver
Dumanis SB, Tesoriero JA, Babus LW, Nguyen MT, Trotter JH, Ladu MJ, et al. ApoE4 decreases spine density and dendritic complexity in cortical neurons in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2009. doi:10.1523/jneurosci.4026-09.2009. PMID: 19955384.
BibTeX
@article{dumanis2009-19955384,
author = {Dumanis, Sonya B and Tesoriero, Joseph A and Babus, Lenard W and Nguyen, Madeline T and Trotter, Justin H and Ladu, Mary Jo and Weeber, Edwin J and Turner, R Scott and others},
title = {{ApoE4 decreases spine density and dendritic complexity in cortical neurons in vivo}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2009},
doi = {10.1523/jneurosci.4026-09.2009},
pmid = {19955384},
url = {https://doi.org/10.1523/jneurosci.4026-09.2009}
}