Spinal fluid of people with Alzheimer’s risk gene signals inflammation

Feb. 18, 2021

People who have a gene variant associated with an increased risk of developing Alzheimer’s disease also tend to have changes in the fluid around their brain and spinal cord that are detectable years before symptoms arise, according to new research from Duke Health as reported in a news release.

The findings, which were published online 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, Duke Health said.

Researchers analyzed data from 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.

Researchers 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.

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