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Spinal Fluid of People with Alzheimer’s Risk Gene Signals Inflammation

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The findings, which were published online last month in the Journal of Alzheimer’s Disease, provide a potential means to identify the earliest mechanisms occurring among APOE4 carriers that might contribute to Alzheimer’s disease before people develop memory problems or other symptoms of dementia. 

Berger and colleagues analyzed data from the targeted cerebrospinal fluid of Alzheimer’s Disease Neuroimaging Institute research participants. Controlling for Alzheimer’s disease clinical status, they identified protein level variations in the cerebrospinal fluid from people with an increasing number of APOE4 gene variant copies. They found that people with more APOE4 copies had lower CRP levels circulating in their cerebrospinal fluid. 

Berger said this is consistent with the current risk profile associated with APOE4 carriers. People with a single APOE4 variant have about a three- to four-fold increased risk of developing Alzheimer’s disease, while those who carry two APOE4 variants have a greater than 10-fold risk. 

Berger said there are other inflammatory diseases for which CRP can be decreased rather than elevated, notably lupus. He said therapies used to control CRP for conditions such as rheumatoid arthritis and vasculitis might warrant investigation for Alzheimer’s disease, but additional studies are needed to further illuminate the Duke team’s findings.

In addition to Berger, study authors include Mary Cooter, Alexander S. Roesler, Stacey Chung, John Park, Jennifer L. Modliszewski, Keith W. VanDusen, J. Will Thompson, Arthur Moseley, Michael J. Devinney, Shayan Smani, Ashley Hall, Victor Cai, Jeffrey N. Browndyke, Michael W. Lutz, David L. Corcoran, and Alzheimer’s Disease Neuroimaging Initiative.

The study received support from the National Institutes of Health (P30AG028716, UH2AG056925, U01 AG024904) the Alzheimer’s Drug Discovery Foundation, the inaugural Ann Bussel award from the Ruth K. Broad Foundation at Duke University, and the Duke Anesthesiology Department. A full listing of supportive funding is provided in the study. 

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Schedule4 Jun 2023