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Subtype-Selective Neuronal Vulnerability and Compensatory Neuroglial Remodeling in Human Cortical Dementia
Roy B, Roy PK.. bioRxiv, 2026-10-11
Topic: Genetics and APOE
Whether the nodal vulnerability in dementia is solely represented by changes in cellular abundance or attrition of cellular transcriptomic landscape attribute to that transition in aging brain is yet to uncover with minutiae. To understand this complication, we have analyzed two snRNA-seq data specific to (I) dorsolateral prefrontal cortex (DLPFC): A comprehensive study of cellular profiling among cognitively normal and pathological ageing and dementia (AD) brain, (II) occipital cortex (OC) in the context of Nasu Hakola disease along with a tissue level bulk RNA-seq data corresponds to temporal cortex. We pinpoint cellular subpopulations their proportional changes within the nodal points and their transcriptomic profiling. In DLPFC we observed alteration of mitochondrial and synaptic maintenance program in the pathological manifestation of disease. In OC we noticed depleted upper layer CUX2 neuron, PVALB and SST neurons on the contrary an enrichment of RORB and LAMP5 neurons with compromised metabolic states in the disease context. Glial populations are marked by representation of fibrous astrocyte, neuronal-supporting subpopulations associated with extracellular matrix remodeling programs. Proportional increment of intermediate myelinating oligodendrocyte and a decrease in mature myelinating subpopulation highlighted a compromised myelin repair attempt. In temporal cortex at tissue level we observed transcriptomic landscape adopted a neuroglial phenotypes in dementia brain. Cell-Chat analysis demonstrated a shift in cellular coordination towards glial population from neuron in NHD brain. A single cell-based drug reprofiling approach identified efatutazone and balaglitazone as broad-spectrum candidates for major cell types in occipital cortex, whereas major actionable biological targets belong to CDK subtypes and proteasome subunits. Overall, our findings imply cellular persistence do not necessarily substantiate molecular preservation, also the coexistence of cellular vulnerability alongside selective remodeling features, present a cellular framework on how to cope up with degenerative changes.
Key findings
- In DLPFC we observed alteration of mitochondrial and synaptic maintenance program in the pathological manifestation of disease.
- Glial populations are marked by representation of fibrous astrocyte, neuronal-supporting subpopulations associated with extracellular matrix remodeling programs.
- In temporal cortex at tissue level we observed transcriptomic landscape adopted a neuroglial phenotypes in dementia brain.
- Cell-Chat analysis demonstrated a shift in cellular coordination towards glial population from neuron in NHD brain.
- Overall, our findings imply cellular persistence do not necessarily substantiate molecular preservation, also the coexistence of cellular vulnerability alongside selective remodeling features, present a cellular framework on how to cope up with degenerative changes.
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. 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 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 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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APA 7th
Roy, B., & Roy, P. K. (2026). Subtype-Selective Neuronal Vulnerability and Compensatory Neuroglial Remodeling in Human Cortical Dementia. bioRxiv. https://doi.org/10.64898/2026.10.03.756274
Vancouver
Roy B, Roy PK. Subtype-Selective Neuronal Vulnerability and Compensatory Neuroglial Remodeling in Human Cortical Dementia. bioRxiv. 2026. doi:10.64898/2026.10.03.756274.
BibTeX
@article{roy2026-2cee5949,
author = {Roy, B. and Roy, P. K.},
title = {{Subtype-Selective Neuronal Vulnerability and Compensatory Neuroglial Remodeling in Human Cortical Dementia}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.03.756274},
url = {https://doi.org/10.64898/2026.10.03.756274}
}