A multitude of genes have been linked to the development of Alzheimer’s disease. Specifically how those genes might influence the progression of neurodegeneration remains something of a black box though, in part because of the challenges of examining in molecular detail the brain of a living patient.
Using cerebrospinal fluid (CSF) collected from living patients, a team of researchers at Washington University School of Medicine in St. Louis has for the first time linked disease-related proteins and genes to identify specific cellular pathways responsible for Alzheimer’s genesis and progression. Because these proteins were gathered from CSF, they are a good proxy for activity in the brain, and several of them may be potential targets for therapies.
The findings are available in Nature Genetics.
The use of patients’ CSF is a step forward for such studies and may be the best way to acquire relevant samples that help map out the constellation of protein activity, known as the proteome, said Carlos Cruchaga, PhD, the Barbara Burton and Reuben Morriss III professor of psychiatry and director of the NeuroGenomics and Informatics Center at WashU Medicine.
“Our goal is to identify risk-linked and protective genes, and also identify the causal role they play,” Cruchaga said. “To do that, we need to study human-derived data. That is why we decided to do a large proteomic study of cerebrospinal fluid, because we know that CSF is a good representation of the pathology of the disease.”
Cruchaga explained that similar investigations have relied on brain tissues collected postmortem, and therefore only provide information about the later stages of Alzheimer’s. Other studies have looked at blood plasma, which is not specific to the tissues affected by the disease.