Shared Transcriptomic Signatures Reveal Synaptic Pruning as a Link Between Alzheimer's Disease and Epilepsy DOI Open Access
Huihong Li, Zhongcong Xie, Yuxuan Tian

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 29, 2024

Abstract Alzheimer’s disease (AD) and epilepsy (EP) exhibit a complex, bidirectional relationship, however, the molecular mechanisms underlying their comorbidity remain poorly understood. To address this gap, we analyzed large-scale transcriptomic datasets from pilocarpine-induced EP mouse models (n = 200), two AD expressing human tau (rTg4510) or amyloid precursor protein (J20) 141), profiles patient cohorts. Differential expression weighted gene co-expression network analyses identified highly conserved immune-related module enriched in microglia-specific genes, particularly Tyrobp , Trem2 C1q complement component genes ( C1qa C1qb C1qc ) implicated synaptic pruning pathway. Gene regulatory analysis showed that regulates these components through . These hub were markedly upregulated both datasets, preserved relationship across species, displayed strong diagnostic value. Cell composition deconvolution single-cell transcriptomics confirmed high, cell-type-specific microglia animal model datasets. Moreover, computational modeling indicated excessive pruning, of inhibitory synapses, alters excitation/inhibition (E/I) balance toward excitability increases neural synchrony. Collectively, our findings reveal how microglial complement-driven synapse elimination may promote seizure activity cognitive decline. We suggest play central role AD, further exploration pathway context provide promising insights into treatment comorbidity. Graphic abstract Highlights Transcriptomic revealed immune module. Shared signatures show value Tyrobp-Trem2-C1q was as shared mechanism Computational E/I synchrony network.

Язык: Английский

Shared Transcriptomic Signatures Reveal Synaptic Pruning as a Link Between Alzheimer's Disease and Epilepsy DOI Open Access
Huihong Li, Zhongcong Xie, Yuxuan Tian

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 29, 2024

Abstract Alzheimer’s disease (AD) and epilepsy (EP) exhibit a complex, bidirectional relationship, however, the molecular mechanisms underlying their comorbidity remain poorly understood. To address this gap, we analyzed large-scale transcriptomic datasets from pilocarpine-induced EP mouse models (n = 200), two AD expressing human tau (rTg4510) or amyloid precursor protein (J20) 141), profiles patient cohorts. Differential expression weighted gene co-expression network analyses identified highly conserved immune-related module enriched in microglia-specific genes, particularly Tyrobp , Trem2 C1q complement component genes ( C1qa C1qb C1qc ) implicated synaptic pruning pathway. Gene regulatory analysis showed that regulates these components through . These hub were markedly upregulated both datasets, preserved relationship across species, displayed strong diagnostic value. Cell composition deconvolution single-cell transcriptomics confirmed high, cell-type-specific microglia animal model datasets. Moreover, computational modeling indicated excessive pruning, of inhibitory synapses, alters excitation/inhibition (E/I) balance toward excitability increases neural synchrony. Collectively, our findings reveal how microglial complement-driven synapse elimination may promote seizure activity cognitive decline. We suggest play central role AD, further exploration pathway context provide promising insights into treatment comorbidity. Graphic abstract Highlights Transcriptomic revealed immune module. Shared signatures show value Tyrobp-Trem2-C1q was as shared mechanism Computational E/I synchrony network.

Язык: Английский

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