Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer's disease
Marcos Otero-Garcia, Sameehan U Mahajani, Debia Wakhloo, Weijing Tang, Yue-Qiang Xue, Samuel Morabito, Jie Pan, Jane Oberhauser et al.. Neuron, 2022-07-25
Topic: Disease mechanisms in lab and animal studies
Tau aggregation in neurofibrillary tangles (NFTs) is closely associated with neurodegeneration and cognitive decline in Alzheimer's disease (AD). However, the molecular signatures that distinguish between aggregation-prone and aggregation-resistant cell states are unknown. We developed methods for the high-throughput isolation and transcriptome profiling of single somas with NFTs from the human AD brain, quantified the susceptibility of 20 neocortical subtypes for NFT formation and death, and identified both shared and cell-type-specific signatures. NFT-bearing neurons shared a marked upregulation of synaptic transmission-related genes, including a core set of 63 genes enriched for synaptic vesicle cycling. Oxidative phosphorylation and mitochondrial dysfunction were highly cell-type dependent. Apoptosis was only modestly enriched, and the susceptibilities of NFT-bearing and NFT-free neurons for death were highly similar. Our analysis suggests that NFTs represent cell-type-specific responses to stress and synaptic dysfunction. We provide a resource for biomarker discovery and the investigation of tau-dependent and tau-independent mechanisms of neurodegeneration.
Key findings
- Tau aggregation in neurofibrillary tangles (NFTs) is closely associated with neurodegeneration and cognitive decline in Alzheimer's disease (AD).
- Our analysis suggests that NFTs represent cell-type-specific responses to stress and synaptic dysfunction.
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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, 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 (Neuron) |
| 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 | 2022 — 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 | 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 35882228) |
| 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
Otero-Garcia, M., Mahajani, S. U., Wakhloo, D., Tang, W., Xue, Y.-Q., Morabito, S., et al. (2022). Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer's disease. Neuron. https://doi.org/10.1016/j.neuron.2022.06.021
Vancouver
Otero-Garcia M, Mahajani SU, Wakhloo D, Tang W, Xue Y.-Q, Morabito S, et al. Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer's disease. Neuron. 2022. doi:10.1016/j.neuron.2022.06.021. PMID: 35882228.
BibTeX
@article{oterogarcia2022-35882228,
author = {Otero-Garcia, Marcos and Mahajani, Sameehan U and Wakhloo, Debia and Tang, Weijing and Xue, Yue-Qiang and Morabito, Samuel and Pan, Jie and Oberhauser, Jane and others},
title = {{Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer's disease}},
journal = {Neuron},
year = {2022},
doi = {10.1016/j.neuron.2022.06.021},
pmid = {35882228},
url = {https://doi.org/10.1016/j.neuron.2022.06.021}
}