Female APOE ε4 Carriers Have Preclinical Signs of Alzheimer's

Changes in brain's memory network can be seen in female carriers before symptoms appear

THURSDAY, June 14 (HealthDay News) -- Healthy elderly women carrying the apolipoprotein E type 4 allele (APOE ε4) show changes in the brain's memory network characteristic of Alzheimer's disease, which can be observed before any symptoms appear, according to a study published in the June 13 issue of The Journal of Neuroscience.

Jessica S. Damoiseaux, Ph.D., from the Stanford University School of Medicine in California, and colleagues performed functional magnetic resonance imaging in 131 healthy elderly adults (median age, 70 years) to assess brain functional connectivity and the association with APOE genotype and gender. They also analyzed data from an independent group of elderly individuals whose levels of tau protein, a marker of Alzheimer's disease, had been measured in their cerebrospinal fluid.

The researchers found that women carrying the ε4 variant showed a loss in the normally synchronized pattern of activity in the network of interconnected regions of the brain's memory network, which they note is a pattern typically seen in Alzheimer's patients. This was particularly prominent in the precuneus, a major default mode hub. Compared with female ε3 homozygotes or male ε4 carriers, female ε4 carriers had significantly lower default mode connectivity, while male ε4 carriers had only a minimal difference. As confirmation, elevated levels of tau protein were found only in women carrying at least one ε4 allele.

"Together, these results converge with previous work showing a higher prevalence of the ε4 allele among women with Alzheimer's disease and, critically, demonstrate that this interaction between APOE genotype and gender is detectable in the preclinical period," Damoiseaux and colleagues conclude.

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