ArticleNeurobiology of aging2024
Elevated protease-activated receptor 4 (PAR4) gene expression in Alzheimer's disease predicts cognitive decline.
Article in Neurobiology of aging, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Review
- Multi-ancestry epigenome wide association study of generalized anxiety disorder.medRxiv : the preprint server for health sciences · 2026Article
- Protease-activated receptor 4 deficiency increases mortality, intracranial bleeding, and blood-brain barrier impairment following traumatic brain injury in mice.Research and practice in thrombosis and haemostasis · 2025Article
- Serine proteases and protease-activated receptors signaling in the kidney.American journal of physiology. Cell physiology · 2025Review
- Exploring SERPINA3 as a neuroinflammatory modulator in Alzheimer's disease with sex and regional brain variations.Metabolic brain disease · 2025Article
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Authors and funding
10 authors.
Funding
Abstract
Platelet activation of protease-activated receptor 4 (PAR4) and thrombin are at the top of a chain of events leading to fibrin deposition, microinfarcts, blood-brain barrier disruption, and inflammation. We evaluated mRNA expression of the PAR4 gene F2RL3 in human brain and global cognitive performance in participants with and without cognitive impairment or dementia. Data were acquired from the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). F2RL3 mRNA was elevated in AD cases and was associated with worse retrospective longitudinal cognitive performance. Moreover, F2RL3 expression interacted with clinical AD diagnosis on longitudinal cognition whereas this relationship was attenuated in individuals without cognitive impairment. Additionally, when adjusting for the effects of AD neuropathology, F2RL3 expression remained a significant predictor of cognitive decline. F2RL3 expression correlated positively with transcript levels of proinflammatory markers including TNFα, IL-1β, NFκB, and fibrinogen α/β/γ. Together, these results reveal that F2RL3 mRNA expression is associated with multiple AD-relevant outcomes and its encoded product, PAR4, may play a role in disease pathogenesis.
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