source: Cardiff University
Researchers have discovered two new genes that increase a person’s risk of developing Alzheimer’s disease.
An international team, including Cardiff University’s Dementia Research Institute, compared 32,000 genetic codes from Alzheimer’s patients and healthy individuals.
The research revealed many new genes and specific mutations in those genes that lead to the development of Alzheimer’s disease. They found rare harmful genetic mutations in genes known as ATP8B4 and ABCA1 that can lead to an increased risk of Alzheimer’s disease.
The researchers also found evidence of genetic alternation in another gene, ADAM10.
Professor Julie Williams, Director of the Institute of Dementia Research at Cardiff University, and co-author of the study, said: “These findings point us towards very specific processing in the brain, which includes differences in the brain’s immune system and how the brain processes cholesterol. These differences affect brain functioning and lead to Alzheimer’s disease progression”.
Alzheimer’s disease is the most common form of dementia in the UK. An estimated 60-80% of the risk of developing Alzheimer’s disease can be explained by genetic factors. For early-onset Alzheimer’s disease (under 65 years of age), this percentage increases to more than 90%.
Professor Williams added: “This study helps expand our knowledge about people at risk of developing this type of dementia. These genetic discoveries also allow us to understand the underlying mechanisms of Alzheimer’s disease, as well as to establish genetic models of the disease to develop targeted therapies in the future – with novel therapies based on on medications or even gene therapy.
The Dementia Research Institute at Cardiff University is well placed to apply this research and advance the development of disease models. We are the largest investment in dementia research in Wales, with over 100 researchers focused on advancing our understanding of dementia and delivering new therapies.
About this genetics and Alzheimer’s disease research news
author: press office
source: Cardiff University
Contact: Press Office – Cardiff University
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“Exome sequencing identifies rare deleterious variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease” by Henne Holstege et al. normal genetics
Exome sequencing identifies rare deleterious variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease
Alzheimer’s disease (AD), the leading cause of dementia, is estimated to be genetically related to about 70%. The genetic component of Alzheimer’s disease has primarily been assessed using genome-wide association studies, which do not capture the risk contributed by rare variants.
Here, we compared the gene-dependent burden of rare deleterious variants in exome sequencing data from 32,558 individuals—16,036 AD cases and 16,522 controls.
next to the variables in TREM2And the SORL1 And the ABCA7we observed a significant association with rare and predicted deleterious variants in ATP8B4 And the ABCA1 With Alzheimer’s risk, a suggestive sign in Adam 10.
In addition, the rare burden in RIN3, CLU, ZCWPW1 And the shred highlighted these genes as potential drivers of AD genome-wide association study loci. Variables associated with the strongest effect on AD risk, particularly loss-of-function variables, are enriched in early-onset AD.
Our results provide further evidence for a key role in amyloid-beta precursor protein processing, amyloid-beta aggregation, lipid metabolism and microglia function in Alzheimer’s disease.