Integrative Genetic and Transcriptomic Analysis Reveals Candidate Molecular Differences Among Dementia with Lewy Bodies, Alzheimer’s Disease, and Parkinson’s Disease Dementia
- 1Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Topkapı, 34093 Istanbul, Turkey
- 2Turkish Health Institutes Presidency (TUSEB), 34718 Istanbul, Turkey
- 3Department of Public Health, Istanbul Faculty of Medicine, Istanbul University, Topkapı, 34093 Istanbul, Turkey
Abstract
Dementia with Lewy bodies (DLB) shares substantial clinical and molecular features with Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD), complicating the identification of disease-specific molecular alterations. This study aimed to characterize transcriptomic differences among these disorders and to integrate expression findings with published Lewy body dementia (LBD) genetic evidence. Gene-level expression profiles from 42 postmortem prefrontal cortex samples in GSE150696, including controls, AD, DLB, and PDD, were analyzed using age- and sex-adjusted empirical-Bayes models with false discovery rate (FDR) correction, followed by sensitivity analyses, post hoc exploratory candidate selection, and integration with an external LBD multi-omics gene-prioritization dataset. No gene reached FDR < 0.05 in the DLB-versus-AD comparison. In contrast, SLC19A2, VAMP1, and COX5B were lower in DLB than in PDD and were FDR-supported in the primary age- and sex-adjusted model, although their statistical significance was partly model-dependent. A post hoc cross-disease analysis identified 60 exploratory candidates, of which SYT11 was the only gene overlapping with the published LBD-prioritized gene set. The overall 60-gene set was not significantly enriched for LBD-associated genes. These findings did not demonstrate broad robust disease–disease differences and are consistent with substantial molecular overlap, while remaining compatible with limited statistical power. A limited number of transcriptomic candidates, including the exploratory SYT11 overlap, warrant independent validation.
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BibTeX
@article{oztan2026integrative,
title = {{Integrative Genetic and Transcriptomic Analysis Reveals Candidate Molecular Differences Among Dementia with Lewy Bodies, Alzheimer’s Disease, and Parkinson’s Disease Dementia}},
author = {Gözde Öztan and Tuğçe İşsever and Halim İşsever},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209173},
url = {https://www.mdpi.com/1422-0067/27/20/9173},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrative Genetic and Transcriptomic Analysis Reveals Candidate Molecular Differences Among Dementia with Lewy Bodies, Alzheimer’s Disease, and Parkinson’s Disease Dementia
AU - Gözde Öztan
AU - Tuğçe İşsever
AU - Halim İşsever
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209173
UR - https://www.mdpi.com/1422-0067/27/20/9173
AB - Dementia with Lewy bodies (DLB) shares substantial clinical and molecular features with Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD), complicating the identification of disease-specific molecular alterations. This study aimed to characterize transcriptomic differences among these disorders and to integrate expression findings with published Lewy body dementia (LBD) genetic evidence. Gene-level expression profiles from 42 postmortem prefrontal cortex samples in GSE150696, including controls, AD, DLB, and PDD, were analyzed using age- and sex-adjusted empirical-Bayes models with false discovery rate (FDR) correction, followed by sensitivity analyses, post hoc exploratory candidate selection, and integration with an external LBD multi-omics gene-prioritization dataset. No gene reached FDR < 0.05 in the DLB-versus-AD comparison. In contrast, SLC19A2, VAMP1, and COX5B were lower in DLB than in PDD and were FDR-supported in the primary age- and sex-adjusted model, although their statistical significance was partly model-dependent. A post hoc cross-disease analysis identified 60 exploratory candidates, of which SYT11 was the only gene overlapping with the published LBD-prioritized gene set. The overall 60-gene set was not significantly enriched for LBD-associated genes. These findings did not demonstrate broad robust disease–disease differences and are consistent with substantial molecular overlap, while remaining compatible with limited statistical power. A limited number of transcriptomic candidates, including the exploratory SYT11 overlap, warrant independent validation.
SN - 1422-0067
ER -