Researchers at Washington University School of Medicine in St. Louis have identified new drug targets for Alzheimer’s disease by studying cerebrospinal fluid (CSF) from living patients.
This fluid, which surrounds the brain and spinal cord, provides insight into brain activity and disease progression, helping scientists pinpoint which proteins and genes are involved in Alzheimer’s.
Their findings, published in Nature Genetics, could pave the way for new therapies.
Alzheimer’s disease has been linked to many genes, but understanding exactly how these genes contribute to the disease remains challenging, partly because it’s difficult to study brain tissue in living patients.
Traditionally, research has relied on postmortem brain samples, which only reveal information about late stages of the disease. Other studies have used blood samples, which are less specific to the brain.
However, CSF offers a more direct way to monitor brain-related protein activity and is a valuable resource for studying Alzheimer’s at various stages.
The research team, led by Dr. Carlos Cruchaga, focused on identifying genes that either increase or decrease Alzheimer’s risk.
They studied a large set of CSF samples from 3,506 individuals, including both healthy people and those with Alzheimer’s, using data from resources like the Knight Alzheimer Disease Research Center and the Dominantly Inherited Alzheimer Network.
By examining CSF proteomics—the study of proteins present in the fluid—they mapped out how certain genes and proteins interact and which pathways in the brain might malfunction during Alzheimer’s.
Dr. Cruchaga explained that just knowing which genes are linked to Alzheimer’s is not enough; understanding the proteins these genes influence is key to grasping the disease’s progression. By linking a person’s genetic data to their proteomic profile, researchers can see which proteins are active and how they contribute to disease.
By comparing CSF samples from people with and without Alzheimer’s, they identified specific proteins associated with disease-related pathways. Of the 6,361 proteins mapped in the CSF, they focused on 1,883 proteins closely related to Alzheimer’s and found that 38 of these proteins likely play a direct role in disease progression, with 15 of them as promising drug targets.
This approach not only identifies proteins that modify Alzheimer’s risk but also reveals the pathways they influence in the brain. Understanding these pathways allows researchers to target the root causes of the disease and develop treatments that may slow or halt its progression.
Dr. Cruchaga and his team are hopeful that these findings will accelerate the development of therapies, not only for Alzheimer’s but for other neurological conditions as well, such as Parkinson’s disease and schizophrenia.
The study also highlights the potential of CSF for exploring other molecules, like metabolites, which are small compounds produced by cellular processes.
In another study published in Nature Genetics, Cruchaga’s team demonstrated that CSF metabolites could be linked to diseases like diabetes and dementia, opening up new avenues for understanding and treating various neurological conditions.
If you care about Alzheimer’s disease, please read studies about the protective power of dietary antioxidants against Alzheimer’s, and eating habits linked to higher Alzheimer’s risk.
For more information about brain health, please see recent studies that oral cannabis extract may help reduce Alzheimer’s symptoms, and Vitamin E may help prevent Parkinson’s disease.
