Spinal Fluid of People With Alzheimer's Risk Gene Signals Inflammation

New research from Duke Health in the Journal of Alzheimer's Disease found carriers of the APOE4 gene variant associated with increased risk of Alzheimer's tend to exhibit changes in the fluid around their brain and spinal cord that can be identified years before symptom manifestation, reports EurekAlert . In such carriers, the cerebrospinal fluid contains lower concentrations of inflammatory molecules called C-reactive proteins (CRP), which suggests that they may be accumulating in the brain and damaging synapses. People with more copies of APOE4 had lower CRP levels in their cerebrospinal fluid, which Duke Professor Miles Berger said aligns with the current risk profile associated with APOE4 carriers. People with one APOE4 variant have about a three- to four-fold elevated risk of developing Alzheimer's disease, while those who carry two APOE4 variants are more than 10 times as susceptible. "We found that spinal fluid CRP levels are lower in people with the APOE4 allele, before they ever develop dementia or even mild cognitive impairment," Berger added. "This suggests that CRP might be actively involved in damaging synapses. We think CRP is doing this together with a cascade of inflammatory proteins called complement, which sequentially activate each other like a row of dominoes falling."