Inflammatory Markers of Alzheimer's Disease Revealed in Spinal Fluid

Spinal fluid (CSF) around the brain and spinal cord tend to show changes in accordance with Alzheimer's disease among people who have a gene variant (APOE4), associated with an increased risk of developing it as per the research at Duke University Medical Center, published in the Journal of Alzheimer's Disease. Alzheimer's disease (AD) is a neurodegenerative disease that leads to gradual memory loss and behavioral changes. It is characterized by the formation of beta-amyloid plaques and the tau proteins in the brain tissues, long before the actual symptoms occur.

A single APOE4 gene variant poses about a three- to four-fold increased risk of developing Alzheimer's disease, and two APOE4 variants have a greater than the 10-fold risk in carriers. APOE4 gene variant is found in around 25% of the population.

The gene variant is associated with a lower level of inflammatory molecules in CSF detectable years before the symptoms appear. This raises the possibility that these inflammatory molecules may be collecting in the brain where they may be damaging synapses, rather than floating freely in the cerebrospinal fluid.

Gene Variant Associated with Alzheimer's Disease

"Our work suggests a potential role for a long-studied molecule called C-reactive protein (CRP), which is typically elevated when there's inflammation, as a factor in the increased Alzheimer's disease risk seen in APOE4 carriers," says lead author Miles Berger, M.D., Ph.D., associate professor in Duke's Department of Anesthesiology.

The study team analyzed data from the targeted cerebrospinal fluid of Alzheimer's Disease Neuroimaging Institute research participants. It was seen that lower CRP levels (inflammatory molecules) circulating in the cerebrospinal fluid were directly associated with increased copies of APOE4 in people (APOE4 carriers).

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The researchers also state that CRP is involved along with a cascade of inflammatory proteins called complement, which sequentially activate each other. These complement pathways as demonstrated in the autopsy brain of AD, can both damage synapses and target them for destruction. This over time, may result in cognitive decline.

"Maybe those with more APOE4 variants have an excessive deletion of synapses throughout life until it gets to the point where the brain can't process information anymore. It would be like taking a book and randomly deleting every 1000th letter. For a while, you could do that and the book would still make sense. But after time, too many letters would be gone and you would lose the information in the book. We think that might be what's happening in the brain", says, Berger.

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The study thereby provides a potential means to identify the earliest mechanisms occurring among APOE4 carriers that might contribute to screening the Alzheimer's disease well in advance.

Source-Medindia