Unlocking the Mystery of Alzheimer’s: Unraveling the Role of New Genes

Published on October 12, 2023

Imagine Alzheimer’s disease as a complex puzzle, with amyloid-beta (Aβ) being the key piece. In this study, scientists set out to uncover additional pieces of the puzzle by identifying genes associated with Aβ uptake in the Korean population. They conducted various tests on 759 participants and discovered six novel genes that displayed a significant association with Aβ uptake in the brain. These genes, including LCMT1 and OSBPL7, play a crucial role in regulating Aβ uptake and have implications for hippocampal volume and cognitive function. Pathway analysis also revealed gene sets related to axon and chemokine activity. By shedding light on these new susceptibility genes, this research brings us one step closer to understanding the underlying mechanisms of Alzheimer’s disease and discovering potential targets for treatment. Want to dive deeper into this groundbreaking study? Check out the link below!

Amyloid-beta (Aβ) is a pathological hallmark of Alzheimer’s disease (AD). We aimed to identify genes related to Aβ uptake in the Korean population and investigate the effects of these novel genes on clinical outcomes, including neurodegeneration and cognitive impairments. We recruited a total of 759 Korean participants who underwent neuropsychological tests, brain magnetic resonance imaging, 18F-flutemetamol positron emission tomography, and microarray genotyping data. We performed gene-based association analysis, and also performed expression quantitative trait loci and network analysis. In genome-wide association studies, no single nucleotide polymorphism (SNP) passed the genome-wide significance threshold. In gene-based association analysis, six genes (LCMT1, SCRN2, LRRC46, MRPL10, SP6, and OSBPL7) were significantly associated with Aβ standardised uptake value ratio in the brain. The three most significant SNPs (rs4787307, rs9903904, and rs11079797) on these genes are associated with the regulation of the LCMT1, OSBPL7, and SCRN2 genes, respectively. These SNPs are involved in decreasing hippocampal volume and cognitive scores by mediating Aβ uptake. The 19 enriched gene sets identified by pathway analysis included axon and chemokine activity. Our findings suggest novel susceptibility genes associated with the uptake of Aβ, which in turn leads to worse clinical outcomes. Our findings might lead to the discovery of new AD treatment targets.

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