Bulk and Single-Nucleus Transcriptomics Highlight Intra-Telencephalic and Somatostatin Neurons in Alzheimer's Disease
Micaela E Consens, Yuxiao Chen, Vilas Menon, Yanling Wang, Julie A Schneider, Philip L De Jager, David A Bennett, Shreejoy J Tripathy et al.. Frontiers in molecular neuroscience, 2022-06-10
Topic: Genetics and APOE
Cortical neuron loss is a pathological hallmark of late-onset Alzheimer's disease (AD). However, it remains unclear which neuronal subtypes beyond broad excitatory and inhibitory classes are most vulnerable. Here, we analyzed cell subtype proportion differences in AD compared to non-AD controls using 1037 post-mortem brain samples from six neocortical regions. We identified the strongest associations of AD with fewer somatostatin (SST) inhibitory neurons (β = -0.48, p bonf = 8.98 × 10-9) and intra-telencephalic (IT) excitatory neurons (β = -0.45, p bonf = 4.32 × 10-7). Replication in three AD case-control single-nucleus RNAseq datasets most strongly supported the bulk tissue association of fewer SST neurons in AD. In depth analyses of cell type proportions with specific AD-related neuropathological and cognitive phenotypes revealed fewer SST neurons with greater brain-wide post-mortem tau and beta amyloid, as well as a faster rate of antemortem cognitive decline. In contrast, greater IT neuron proportions were associated with a slower rate of cognitive decline as well as greater residual cognition-a measure of cognitive resilience-but not canonical AD neuropathology. Our findings implicate somatostatin inhibitory and intra-telencephalic excitatory neuron subclasses in the pathogenesis of AD and in cognitive resilience to AD pathology, respectively.
Key findings
- Here, we analyzed cell subtype proportion differences in AD compared to non-AD controls using 1037 post-mortem brain samples from six neocortical regions.
- In depth analyses of cell type proportions with specific AD-related neuropathological and cognitive phenotypes revealed fewer SST neurons with greater brain-wide post-mortem tau and beta amyloid, as well as a faster rate of antemortem cognitive decline.
- In contrast, greater IT neuron proportions were associated with a slower rate of cognitive decline as well as greater residual cognition-a measure of cognitive resilience-but not canonical AD neuropathology.
- Our findings implicate somatostatin inhibitory and intra-telencephalic excitatory neuron subclasses in the pathogenesis of AD and in cognitive resilience to AD pathology, respectively.
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Study details
- Study designcase-control study
- Evidence strengthModerate
How this study scored 55/100
Published in a peer-reviewed journal, and it is a case-control study. Scored zero for 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 31 of the 56 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in molecular neuroscience) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 6 / 12 | A case-control study |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 35754708) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 31 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 31 of the 56 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
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APA 7th
Consens, M. E., Chen, Y., Menon, V., Wang, Y., Schneider, J. A., De Jager, P. L., et al. (2022). Bulk and Single-Nucleus Transcriptomics Highlight Intra-Telencephalic and Somatostatin Neurons in Alzheimer's Disease. Frontiers in molecular neuroscience. https://doi.org/10.3389/fnmol.2022.903175
Vancouver
Consens ME, Chen Y, Menon V, Wang Y, Schneider JA, De Jager PL, et al. Bulk and Single-Nucleus Transcriptomics Highlight Intra-Telencephalic and Somatostatin Neurons in Alzheimer's Disease. Frontiers in molecular neuroscience. 2022. doi:10.3389/fnmol.2022.903175. PMID: 35754708.
BibTeX
@article{consens2022-35754708,
author = {Consens, Micaela E and Chen, Yuxiao and Menon, Vilas and Wang, Yanling and Schneider, Julie A and De Jager, Philip L and Bennett, David A and Tripathy, Shreejoy J and others},
title = {{Bulk and Single-Nucleus Transcriptomics Highlight Intra-Telencephalic and Somatostatin Neurons in Alzheimer's Disease}},
journal = {Frontiers in molecular neuroscience},
year = {2022},
doi = {10.3389/fnmol.2022.903175},
pmid = {35754708},
url = {https://doi.org/10.3389/fnmol.2022.903175}
}