Key result
Shared dysregulated genes in lipid and vascular pathways link cardiovascular disease risk to Alzheimer's disease.
Why the study?
CVD and Alzheimer's disease often co-occur and appear to increase risk for each other, but the exact relationship and underlying overlapping genetics remain uncertain.
This scoping review demonstrates that cardiovascular disease and Alzheimer's disease share genetic underpinnings and mechanistic pathways, notably involving lipid metabolism, blood pressure regulation, and blood-brain barrier integrity.
Does not yet support practice changes in CVD or AD; extends shared pathway hypotheses pending longitudinal diverse cohort validation.
BACKGROUND/OBJECTIVES: Cardiovascular disease (CVD) and Alzheimer's disease (AD) are two diseases highly prevalent in the aging population and often co-occur. The exact relationship between the two diseases is uncertain, though epidemiological studies have demonstrated that CVDs appear to increase the risk of AD and vice versa. This scoping review aims to examine the current identified overlapping genetics between CVDs and AD at the individual gene level and at the shared pathway level. METHODS: Following PRISMA-ScR guidelines for a scoping review, we searched the PubMed and Scopus databases from 1990 to October 2024 for articles that involved (1) CVDs, (2) AD, and (3) used statistical methods to parse genetic relationships. RESULTS: reportedly have wide effects across the AD and CVD spectrum, affecting both cardiac and brain tissues. Mechanistically, changes in three main pathways (lipid metabolism, blood pressure regulation, and the breakdown of the blood-brain barrier (BBB)) contribute to subclinical and etiological changes that promote both AD and CVD progression. However, genetic studies continue to be limited by the availability of longitudinal data and lack of cohorts that are representative of diverse populations. CONCLUSIONS: Highly penetrant familial genes simultaneously increase the risk of CVDs and AD. However, in most cases, sets of dysregulated genes within larger-scale mechanisms, like changes in lipid metabolism, blood pressure regulation, and BBB breakdown, increase the risk of both AD and CVDs and contribute to disease progression.
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Moore et al. (2024) conducted a review in Cardiovascular Disease and Alzheimer's Disease (n=274). Shared genetic factors and biological pathways (lipid metabolism, blood pressure, BBB breakdown) was evaluated on Overlapping genetics between CVDs and AD at the individual gene level and shared pathway level. Dysregulated genes within shared pathways, including lipid metabolism, blood pressure regulation, and blood-brain barrier breakdown, simultaneously increase the risk and progression of both cardiovascular disease and Alzheimer's disease.
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