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Characterizing molecular and synaptic signatures in mouse models of late-onset Alzheimer's disease independent of amyloid and tau pathology
Kotredes KP, Pandey RS, Persohn S, Elderidge K, Burton CP, Miner EW, Haynes KA, Santos DFS et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024-05-12
Topic: Amyloid, tau and blood-test diagnosis
Introduction MODEL-AD (Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease) is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to capture the trajectory and progression of late-onset Alzheimer's disease (LOAD) more accurately. Methods We created the LOAD2 model by combining apolipoprotein E4 (APOE4), Trem2*R47H, and humanized amyloid-beta (Aβ). Mice were subjected to a control diet or a high-fat/high-sugar diet (LOAD2+HFD). We assessed disease-relevant outcome measures in plasma and brain including neuroinflammation, Aβ, neurodegeneration, neuroimaging, and multi-omics. Results By 18 months, LOAD2+HFD mice exhibited sex-specific neuron loss, elevated insoluble brain Aβ42, increased plasma neurofilament light chain (NfL), and altered gene/protein expression related to lipid metabolism and synaptic function. Imaging showed reductions in brain volume and neurovascular uncoupling. Deficits in acquiring touchscreen-based cognitive tasks were observed. Discussion The comprehensive characterization of LOAD2+HFD mice reveals that this model is important for preclinical studies seeking to understand disease trajectory and progression of LOAD prior to or independent of amyloid plaques and tau tangles. Highlights By 18 months, unlike control mice (e.g., LOAD2 mice fed a control diet, CD), LOAD2+HFD mice presented subtle but significant loss of neurons in the cortex, elevated levels of insoluble Ab42 in the brain, and increased plasma neurofilament light chain (NfL). Transcriptomics and proteomics showed changes in gene/proteins relating to a variety of disease-relevant processes including lipid metabolism and synaptic function. In vivo imaging revealed an age-dependent reduction in brain region volume (MRI) and neurovascular uncoupling (PET/CT). LOAD2+HFD mice also demonstrated deficits in acquisition of touchscreen-based cognitive tasks.
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APA 7th
Kotredes, K. P., Pandey, R. S., Persohn, S., Elderidge, K., Burton, C. P., Miner, E. W., et al. (2024). Characterizing molecular and synaptic signatures in mouse models of late-onset Alzheimer's disease independent of amyloid and tau pathology. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.13828
Vancouver
Kotredes KP, Pandey RS, Persohn S, Elderidge K, Burton CP, Miner EW, et al. Characterizing molecular and synaptic signatures in mouse models of late-onset Alzheimer's disease independent of amyloid and tau pathology. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. doi:10.1002/alz.13828. PMID: 38735056.
BibTeX
@article{kotredes2024-38735056,
author = {Kotredes, K. P. and Pandey, R. S. and Persohn, S. and Elderidge, K. and Burton, C. P. and Miner, E. W. and Haynes, K. A. and Santos, D. F. S. and others},
title = {{Characterizing molecular and synaptic signatures in mouse models of late-onset Alzheimer's disease independent of amyloid and tau pathology}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2024},
doi = {10.1002/alz.13828},
pmid = {38735056},
url = {https://doi.org/10.1002/alz.13828}
}
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Key findings
- Results By 18 months, LOAD2+HFD mice exhibited sex-specific neuron loss, elevated insoluble brain Aβ42, increased plasma neurofilament light chain (NfL), and altered gene/protein expression related to lipid metabolism and synaptic function.
- Highlights By 18 months, unlike control mice (e.g., LOAD2 mice fed a control diet, CD), LOAD2+HFD mice presented subtle but significant loss of neurons in the cortex, elevated levels of insoluble Ab42 in the brain, and increased plasma neurofilament light chain (NfL).
- In vivo imaging revealed an age-dependent reduction in brain region volume (MRI) and neurovascular uncoupling (PET/CT).
- LOAD2+HFD mice also demonstrated deficits in acquisition of touchscreen-based cognitive tasks.
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Study details
- Evidence strengthLow
How this study scored 48/100
Published in a leading specialty 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 and multi-centre collaboration, so those were left out: it earned 28 of the 58 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| 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 | 4 / 5 | 2024 — within 3 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 38735056) |
| Free to read | 2 / 2 | Free to read |
| Points | 28 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 28 of the 58 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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