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People with memory complaints, Alzheimer's risk gene show early biological signs of disease

Cognitively normal older adults who report memory problems and have a genetic risk for late-onset Alzheimer’s disease also have biological evidence of brain changes associated with the disease, a new NIA-funded study reports. The findings tentatively identify a group at risk for developing Alzheimer’s who might benefit from intervention many years before symptoms appear. The study was published online May 7, 2015, in Alzheimer’s & Dementia.

Researchers led by Dr. Andrew J. Saykin of Indiana University School of Medicine, Indianapolis, used data from the NIA-supported Alzheimer’s Disease Neuroimaging Initiative (ADNI), to analyze Alzheimer’s biomarker measurements and neuroimaging results from 594 older adults. The volunteers were classified into three groups: cognitively normal, significant memory concerns (SMC), and early mild cognitive impairment. The researchers were especially interested in a sample of 90 adults with SMC, whose memory concerns were reported by themselves but not by family members or friends.

People with SMC who carry the well-known APOE ɛ4 genetic risk factor for late-onset Alzheimer’s had more biomarker evidence of changes linked to the disease than SMC participants without APOE ɛ4, the researchers found. This biomarker evidence consisted of greater deposits of the beta amyloid protein in the brain, found using amyloid PET imaging, and lower levels of beta-amyloid 1-42 and higher levels of tau, another protein associated with Alzheimer’s, found in cerebrospinal fluid. However, other signs of possible Alzheimer’s disease—lowered brain glucose activity and medial temporal lobe shrinkage—were not associated with APOE carrier status.

The findings help confirm the influence of APOE ε4 carrier status on Alzheimer’s biomarkers years before symptoms may appear and the importance of beta amyloid accumulation as one of the earliest measurable changes of the disease process.

Reference: Saykin A.J., et al., APOE effects on Alzheimer’s biomarkers in older adults with significant memory concerns. Alzheimer’s & Dementia. May 7, 2015; doi: 10.1016/j.jalz.2015.03.003.