Study: Cerebrospinal fluid in patients with Alzheimer’s disease shows a risk of genetic inflammation

In a clinical study by researchers at Duke University School of Medicine, people with genetic mutations associated with an increased risk of developing Alzheimer’s disease also have body fluids around the cerebrum and spinal cord that can be recognized years before symptoms appear. Claims that there is a tendency for change.

We found that people with the APOE4 gene variant, found in about 25% of the population, had low levels of certain inflammatory molecules in the cerebrospinal fluid. This increases the likelihood that these inflammatory molecules are not floating freely in the cerebrospinal fluid, but are concentrated in the brain, which can damage synapses.

Findings published in the Journal of Alzheimer’s Disease identify the earliest mechanisms that occur among APOE4 carriers that may contribute to Alzheimer’s disease before people develop memory loss and other symptoms of dementia. It provides a potential means of doing so.

“Our study has shown that a long-studied molecule called C-reactive protein (CRP), which normally increases with inflammation, is a potential factor in the increased risk of Alzheimer’s disease seen in APOE4 carriers. It suggests a role, “said lead author Miles Berger. , MD, Ph.D. , Associate Professor of Duke Anesthesiology.

Berger et al. Analyzed data from targeted cerebrospinal fluid from research participants at the Alzheimer’s Disease Neuroimaging Institute. They managed the clinical status of Alzheimer’s disease and identified changes in cerebrospinal fluid protein levels in people with increased copy numbers of APOE4 gene variants. They found that people with high copies of APOE4 had low levels of CRP circulating in the cerebrospinal fluid.

Berger said this is consistent with the current risk profile associated with APOE4 carriers. People with one APOE4 mutant are about 3-4 times more likely to develop Alzheimer’s disease, while people with two APOE4 mutants are more than 10 times more at risk.

“People with the APOE4 allele were found to have low CRP levels in the cerebrospinal fluid before they developed dementia or mild cognitive impairment,” Berger said. “This suggests that CRP may be actively involved in synaptic damage. CRP is an inflammatory protein called complement that sequentially activates each other so that domino rows fall. I think you’re doing this with the Cascade of.

“Autopsy of the brains of patients suffering from Alzheimer’s disease also show changes in complement activity, and complement pathways can damage synapses and become targets for destruction,” Berger said. “Our results show that these processes in APOE4 carriers can function for years and even decades, ultimately leading to a decline in Alzheimer’s disease and cognitive decline. I’m raising it. “

Berger said there are other inflammatory diseases, especially lupus, where CRP can decrease rather than increase. He added that therapies used to control CRP for conditions such as rheumatoid arthritis and vasculitis may justify the investigation of Alzheimer’s disease, but to further clarify the Duke team’s findings. Said that research is needed.

“Probably, people with a lot of APOE4 mutants have excessive synapses removed throughout their lives until the brain can’t process the information,” Berger said. “It’s like taking a book and randomly deleting it every 1000 characters. You could do that for a while and the book still makes sense. But over time, too many characters disappear. And the information in the book is lost .. We think it may be happening in the brain. ”

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