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Selective vulnerability: validation of atypical neurodegenerative disease variants in histopathological reference cohorts
Geser F.. Research Square, 2026-10-16
Topic: Genetics and APOE
Conventional, cohort-based staging exhibited profound topographical inversion, yielding negative correlations for TDP-43 ( ρ = -0.9113, p < 0.001) and α-synuclein ( ρ = -0.8660, p = 0.003) sub-cohorts. Conversely, the novel OPC system resolved this mismatch, reversing the correlation into a highly precise positive range (TDP-43: ρ = 0.9113, p < 0.001, R 2 = 0.83; α-synuclein: ρ = 0.8660, p = 0.003, R 2 = 0.75). In the combined pool ( N = 18 data pairs), the OPC model achieved strong global validation ( ρ = 0.8825, p < 0.001, R 2 = 0.78; Steiger Z = -6.497, p < 0.0001). Individual anchoring demonstrated absolute topological consistency ( J = 1.00). Atypical variants are not statistical outliers but topographically determined systemic states reflecting inherent CNS vulnerability. Clinical anomalies serve as highly sensitive, topographically anchored early indicators ("red flags") of underlying proteinopathies.
Key findings
- Conventional, cohort-based staging exhibited profound topographical inversion, yielding negative correlations for TDP-43 ( ρ = -0.9113, p < 0.001) and α-synuclein ( ρ = -0.8660, p = 0.003) sub-cohorts.
- Conversely, the novel OPC system resolved this mismatch, reversing the correlation into a highly precise positive range (TDP-43: ρ = 0.9113, p < 0.001, R 2 = 0.83; α-synuclein: ρ = 0.8660, p = 0.003, R 2 = 0.75).
- In the combined pool ( N = 18 data pairs), the OPC model achieved strong global validation ( ρ = 0.8825, p < 0.001, R 2 = 0.78; Steiger Z = -6.497, p < 0.0001).
- Individual anchoring demonstrated absolute topological consistency ( J = 1.00).
- Atypical variants are not statistical outliers but topographically determined systemic states reflecting inherent CNS vulnerability.
Study details
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 24 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 15 of the 62 points we could judge it on, which is 24 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| 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 | 3 / 5 | Rated “moderate” 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 | 15 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 15 of the 62 points we could judge it on is 24 out of 100. |
| Total | 24 / 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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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Geser, F. (2026). Selective vulnerability: validation of atypical neurodegenerative disease variants in histopathological reference cohorts. Research Square. https://doi.org/10.21203/rs.3.rs-11296547/v1
Vancouver
Geser F. Selective vulnerability: validation of atypical neurodegenerative disease variants in histopathological reference cohorts. Research Square. 2026. doi:10.21203/rs.3.rs-11296547/v1.
BibTeX
@article{geser2026-38cff4ba,
author = {Geser, F.},
title = {{Selective vulnerability: validation of atypical neurodegenerative disease variants in histopathological reference cohorts}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-11296547/v1},
url = {https://doi.org/10.21203/rs.3.rs-11296547/v1}
}
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