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Genetic Factors Responsible for Alzheimer's Disease Identified

By LabMedica International staff writers
Posted on 16 Jan 2018
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Image: Researchers have identified genes that could be precursors to Alzheimer’s disease, which could be targets for new treatments that may delay or prevent the onset of the disease (Photo courtesy of Medical News Today).
Image: Researchers have identified genes that could be precursors to Alzheimer’s disease, which could be targets for new treatments that may delay or prevent the onset of the disease (Photo courtesy of Medical News Today).
Several new genes have been identified that are responsible for Alzheimer's disease (AD) including those leading to functional and structural changes in the brain and elevated levels of AD proteins in cerebrospinal fluid (CSF).

A new study focused on individual groups across specific on the cognitive spectrum: normal cognitive functioning or controls, mild cognitive impairment (MCI) and AD cases. As opposed to the typical study design, which combines all such persons into a single group or focuses only on cognitively healthy persons, a new study identified several novel genetic associations within multiple subgroups.

A team of scientists led by those at Boston University School of Medicine (Boston, MA, USA) conducted genome-wide association studies for AD-related endophenotypes including hippocampal volume, logical memory scores, and CSF. They tested the association between AD-related brain MRI measures, logical memory test scores and CSF levels of two AD proteins amyloid-beta (Aβ42) and tau with several million genetic markers called single-nucleotide polymorphisms (SNPs) across the genome in a sample of 1,189 participants of the Alzheimer Disease Neuroimaging Initiative (ADNI) study. They then examined the biological significance of the top-ranked associated SNPs and genes using several datasets containing information about gene expression in parts of the brain most affected by AD.

The scientists found that two of the study-wide significant genes identified in the normal cognitive functioning group, Serine/Arginine Repetitive Matrix 4 (SRRM4) and Microtubule Associated Scaffold Protein 1(MTUS1), are involved in neuronal signaling, development and loss. Another gene identified in this group, Glutamate Ionotropic Receptor NMDA Type Subunit 2B (GRIN2B), encodes a subunit of a receptor that has roles in resilience of neurons and memory. They found consistent expression patterns of C14orf40 and MTUS1 in carriers with risk alleles of expression SNPs and in brains of AD patients, compared with in the noncarriers and in brains of controls.

Lindsay A. Farrer, PhD, Distinguished Professor of Genetics and principal investigator of the study, said, “Our findings provide important insight about biological mechanisms leading to Alzheimer disease, especially at stages of the disease before symptoms occur. The novel genes we identified may be potential targets for developing new treatments that might delay or even prevent onset of symptoms of this insidious disease.” The study was published on December 20, 2017, in the journal Alzheimer's & Dementia.

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Boston University School of Medicine

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