Genes that trigger Alzheimer's disease (AD) and those that lead to functional and structural changes in the brain have been identified. They are also responsible for elevated levels of AD proteins in cerebrospinal fluid (CSF).
Unlike traditional AD research, the 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, this research identified several novel genetic associations within multiple subgroups.
According to the researchers, these associations are not evident when comparing AD cases to controls or within AD cases, suggesting that these signals underlie processes before the onset of AD. As such, these genes may be more attractive targets for drug development because it is increasingly recognized that effective drugs will be those given to persons before or shortly after they develop cognitive impairment.
Two of the study-wide significant genes identified in the normal cognitive functioning group, SRRM4 and MTUS1, are involved in neuronal signaling, development, and loss. Another gene identified in this group, GRIN2B, encodes a subunit of a receptor that has roles in the resilience of neurons and memory.
"Our findings provide important insight about biological mechanisms leading to Alzheimer disease, especially at stages of the disease before symptoms occur," says Lindsay A. Farrer, PhD, Distinguished Professor of Genetics and Chief of the Biomedical Genetics section at Boston University School of Medicine, and principal investigator of the study.
"The novel genes we identified may be potential targets for developing new treatments that might delay or even prevent the onset of symptoms of this insidious disease."