Endocannabinoid System Genes in Dementia: A Systematic Mendelian Randomization Study of Functional Variants and Tissue-Specific Expression Across Clinical, Molecular, and Neuroimaging Phenotypes

· 2026-09-10 · 原文

DOI：10.64898/2026.09.08.26362514v1?rss=1

Background: Dementia is a leading cause of disability and death worldwide, and despite substantial research investment, disease-modifying treatments remain limited. The endocannabinoid system (ECS) has emerged as a promising candidate pathway, regulating key neurobiological processes implicated in dementia, including neuroinflammation, synaptic transmission, and cerebrovascular function. However, evidence linking ECS genetic variation to dementia risk in humans remains limited. Methods: We conducted a systematic Mendelian randomization (MR) investigation of seven ECS genes (CNR1, CNR2, FAAH, DAGLA, DAGLB, NAPEPLD, MGLL) in relation to Alzheimer's disease (AD), vascular dementia (VasD), and all-cause dementia. Primary analyses evaluated putatively functional variants within these genes, fol

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1. 人话版

Background: Dementia is a leading cause of disability and death worldwide, and despite substantial research investment, disease-modifying treatments remain limited.

The endocannabinoid system (ECS) has emerged as a promising candidate pathway, regulating key neurobiological processes implicated in dementia, including neuroinflammation, synaptic transmission, and cerebrovascular function.

2. 领域脉络

来源板块：板块一 · 研究前沿。

3. 机制拆解

Primary analyses evaluated putatively functional variants within these genes, fol

4. 证据与数字

Methods: We conducted a systematic Mendelian randomization (MR) investigation of seven ECS genes (CNR1, CNR2, FAAH, DAGLA, DAGLB, NAPEPLD, MGLL) in relation to Alzheimer's disease (AD), vascular dementia (VasD), and all-cause dementia.

5. 反例与边界

However, evidence linking ECS genetic variation to dementia risk in humans remains limited.

6. 跨领域连接与意外收获

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