ApoE epsilon(4) Allele Related Alterations in Hippocampal Connectivity in Early Alzheimer%26apos;s Disease Support Memory Performance

作者：De Marco Matteo; Vallelunga Annamaria; Meneghello Francesca; Varma Susheel; Frangi Alejandro F; Venneri Annalena

来源：Current Alzheimer Research, 2017, 14(7): 766-777.

DOI：10.2174/1567205014666170206113528

• Functional connectivity
• disinhibition hypothesis
• posterior cingulate
• hippocampus
• Alzheimer's disease
• network disruption

Background: Whether the presence of the Apolipoprotein E epsilon(4) allele modulates hippocampal connectivity networks in abnormal ageing has yet to be fully clarified.
Objective: Allele-dependent differences in this pattern of functional connectivity were investigated in patients with very mild neurodegeneration of the Alzheimer's type, carriers and non-carriers of the epsilon(4) allele.
Method: A seed-based connectivity approach was used. The two groups were similar in demographics, volumetric measures of brain structure, and cognitive profiles.
Results: epsilon(4)-carriers had increased connectivity between the seed area in the left hippocampus and 1) a left insular/lateral prefrontal region and 2) the contralateral right parietal cortex. Moreover, hippocampus-to-parietal connectivity in the group of epsilon(4) carriers was positively associated with memory performance, indicating that the between-group difference reflects compensatory processes. Retrospective analyses of functional connectivity based on patients from the ADNI initiative confirmed this pattern.
Conclusion: We suggest that increased connectivity with areas external to the Default Mode Network (DMN) reflects both compensatory recruitment of additional areas, and pathological interwining between the DMN and the salience network as part of a global epsilon(4)-dependent circuital disruption. These differences indicate that the epsilon(4) allele is associated with a more profound degree of DMN network breakdown even in the prodromal stage of neurodegeneration.

• 出版日期2017