Apolipoprotein E isoform does not influence trans-synaptic spread of tau pathology in a mouse model
Caitlin Davies, Jane Tulloch, Ellie Yip, Lydia Currie, Marti Colom-Cadena, Susanne Wegmann, Bradley T Hyman, Lewis Wilkins et al.. Brain and neuroscience advances, 2023-08-17
Topic: Disease mechanisms in lab and animal studies
A key hallmark of Alzheimer's disease (AD) is the accumulation of hyperphosphorylated tau in neurofibrillary tangles. This occurs alongside neuroinflammation and neurodegeneration. Pathological tau propagates through the AD brain in a defined manner, which correlates with neuron and synapse loss and cognitive decline. One proposed mechanism of tau spread is through synaptically connected brain structures. Apolipoprotein E4 (APOE4) genotype is the strongest genetic risk factor for late-onset AD and is associated with increased tau burden. Whether the apolipoprotein E (APOE) genotype influences neurodegeneration via tau spread is currently unknown. Here, we demonstrate that virally expressed human tau (with the P301L mutation) injected into mouse entorhinal cortex at 5-6 months or 15-16 months of age spreads trans-synaptically to the hippocampus by 14 weeks post-injection. Injections of tau in mice expressing human APOE2, APOE3 or APOE4, as well as APOE knock-outs, showed that tau can spread trans-synaptically in all genotypes and that APOE genotype and age do not affect the spread of tau. These data suggest that APOE genotype is not directly linked to synaptic spread of tau in our model, but other mechanisms involving non-cell autonomous manners of tau spread are still possible.
Key findings
- Apolipoprotein E4 (APOE4) genotype is the strongest genetic risk factor for late-onset AD and is associated with increased tau burden.
- Injections of tau in mice expressing human APOE2, APOE3 or APOE4, as well as APOE knock-outs, showed that tau can spread trans-synaptically in all genotypes and that APOE genotype and age do not affect the spread of tau.
- These data suggest that APOE genotype is not directly linked to synaptic spread of tau in our model, but other mechanisms involving non-cell autonomous manners of tau spread are still possible.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, 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 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 (Brain and neuroscience advances) |
| 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 | 2023 — within 6 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 | Laboratory or animal study (title names “mouse”) — scores zero |
| 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 37600228) |
| 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
Davies, C., Tulloch, J., Yip, E., Currie, L., Colom-Cadena, M., Wegmann, S., et al. (2023). Apolipoprotein E isoform does not influence trans-synaptic spread of tau pathology in a mouse model. Brain and neuroscience advances. https://doi.org/10.1177/23982128231191046
Vancouver
Davies C, Tulloch J, Yip E, Currie L, Colom-Cadena M, Wegmann S, et al. Apolipoprotein E isoform does not influence trans-synaptic spread of tau pathology in a mouse model. Brain and neuroscience advances. 2023. doi:10.1177/23982128231191046. PMID: 37600228.
BibTeX
@article{davies2023-37600228,
author = {Davies, Caitlin and Tulloch, Jane and Yip, Ellie and Currie, Lydia and Colom-Cadena, Marti and Wegmann, Susanne and Hyman, Bradley T and Wilkins, Lewis and others},
title = {{Apolipoprotein E isoform does not influence trans-synaptic spread of tau pathology in a mouse model}},
journal = {Brain and neuroscience advances},
year = {2023},
doi = {10.1177/23982128231191046},
pmid = {37600228},
url = {https://doi.org/10.1177/23982128231191046}
}