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16/100

⚠ Preprint — not yet peer-reviewed alzhub usefulness score 16 out of 100. Lewy body dementia

Topic: Brain proteins, microglia and lab models

ResultsThe CNR2 missense variant rs4649124 was associated with increased vascular dementia risk (BH-adjusted P = 0.049) after correction at the 5% false discovery rate (FDR) threshold, with additional associations at the 10% FDR threshold for all-cause dementia risk (BH-adjusted P = 0.051) and lower circulating APP (BH-adjusted P = 0.088) and BDNF (BH-adjusted P = 0.083) levels. The FAAH missense variant rs324420 was associated with lower circulating BDNF levels (BH-adjusted P = 0.037) after multiple testing correction. The CNR1 missense variant rs12720071 was associated with reduced bilateral hippocampal volume (BH-adjusted P = 0.095), whereas the DAGLB functional variant rs1055430 showed no evidence of association with any of the outcomes examined (BH-adjusted P > 0.2). Higher cortical MGLL expression was additionally associated with increased all-cause dementia risk at the 10% FDR threshold (BH-adjusted P = 0.091). However, several biologically plausible associations were identified, particularly involving CNR2, FAAH, CNR1, and DAGLB, suggesting that selected ECS components may influence neuroinflammatory, neurotrophic, cerebrovascular, and structural brain pathways relevant to dementia. Although colocalization analyses did not support shared causal variants, these findings highlight candidate neurobiological pathways that warrant further investigation in larger, well-powered genetic and functional studies.

Key findings

ResultsThe CNR2 missense variant rs4649124 was associated with increased vascular dementia risk (BH-adjusted P = 0.049) after correction at the 5% false discovery rate (FDR) threshold, with additional associations at the 10% FDR threshold for all-cause dementia risk (BH-adjusted P = 0.051) and lower
The FAAH missense variant rs324420 was associated with lower circulating BDNF levels (BH-adjusted P = 0.037) after multiple testing correction.
The CNR1 missense variant rs12720071 was associated with reduced bilateral hippocampal volume (BH-adjusted P = 0.095), whereas the DAGLB functional variant rs1055430 showed no evidence of association with any of the outcomes examined (BH-adjusted P > 0.2).
Higher cortical MGLL expression was additionally associated with increased all-cause dementia risk at the 10% FDR threshold (BH-adjusted P = 0.091).
However, several biologically plausible associations were identified, particularly involving CNR2, FAAH, CNR1, and DAGLB, suggesting that selected ECS components may influence neuroinflammatory, neurotrophic, cerebrovascular, and structural brain pathways relevant to dementia.

Why it matters

This genetic study found some associations between endocannabinoid system gene variants and dementia risk, brain volume, and protein levels, but colocalization analyses did not support shared causal variants. It highlights candidate pathways for further research, not a treatment, cure, or prevention.

Study details

Evidence strengthLow

How this study scored 16/100

Preprint — not yet peer-reviewed. It scored 23 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 impact for its field and year, so that was left out: it earned 22 of the 94 points we could judge it on, which is 23 out of 100.

Component	Points	Why
Journal tier	2 / 10	Tier 4 — not a peer-reviewed journal (medRxiv (preprint))
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	0 / 7	Cited 0 times (OpenAlex, 2026-10-10)
Citations per year	0 / 5	0.0 citations a year over 2 year(s) since 2026
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	0 / 6	No other study in this library cites it
Still being cited	0 / 4	Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	3 / 4	Last-listed author Sagnik Bhattacharyya: h-index 59 (OpenAlex, whole career)
Institution's track record	2 / 3	University of Cambridge: institution h-index 1,973 (OpenAlex)
Multi-centre collaboration	2 / 3	OpenAlex lists 4 institution(s) in 1 country
Indexed in PubMed	1 / 2	Not in PubMed, but has a DOI
Free to read	2 / 2	Free to read
Points	22 / 94	Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 22 of the 94 points we could judge it on is 23 out of 100.
Total	23 / 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

Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.

APA 7th

Javidnia, S., Karhunen, V., Woolf, B., Burgess, S., Proitsi, P., Velayudhan, L., et al. (2026). Endocannabinoid System Genes in Dementia: A Systematic Mendelian Randomization Study of Functional Variants and Tissue-Specific Expression Across Clinical, Molecular, and Neuroimaging Phenotypes. medRxiv (preprint). https://doi.org/10.64898/2026.09.08.26362514

Vancouver

Javidnia S, Karhunen V, Woolf B, Burgess S, Proitsi P, Velayudhan L, et al. Endocannabinoid System Genes in Dementia: A Systematic Mendelian Randomization Study of Functional Variants and Tissue-Specific Expression Across Clinical, Molecular, and Neuroimaging Phenotypes. medRxiv (preprint). 2026. doi:10.64898/2026.09.08.26362514.

BibTeX

@article{javidnia2026-df90200c,
  author  = {Javidnia, S. and Karhunen, V. and Woolf, B. and Burgess, S. and Proitsi, P. and Velayudhan, L. and Bhattacharyya, S.},
  title   = {{Endocannabinoid System Genes in Dementia: A Systematic Mendelian Randomization Study of Functional Variants and Tissue-Specific Expression Across Clinical, Molecular, and Neuroimaging Phenotypes}},
  journal = {medRxiv (preprint)},
  year    = {2026},
  doi     = {10.64898/2026.09.08.26362514},
  url     = {https://doi.org/10.64898/2026.09.08.26362514}
}

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