ApoE ε4 Allele Related Alterations in Hippocampal Connectivity in Early Alzheimer's Disease Support Memory Performance.
Whether the presence of the Apolipoprotein E ε4 allele modulates hippocampal connectivity networks in abnormal ageing has yet to be fully clarified.



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 ε4 allele.



A seed-based connectivity approach was used. The two groups were similar in demographics, volumetric measures of brain structure, and cognitive profiles.



ε4-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 ε4 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.



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 ε4-dependent circuital disruption. These differences indicate that the ε4 allele is associated with a more profound degree of DMN network breakdown even in the prodromal stage of neurodegeneration.
Department of Neuroscience, University of Sheffield, Sheffield. United Kingdom.
Matteo
M
De Marco
Neuroscience Section, Department of Medicine and Surgery, Center for Neurodegenerative Diseases (CEMAND), University of Salerno, Salerno. Italy.
Annamaria
A
Vallelunga
Fondazione Ospedale San Camillo, Venice. Italy.
Francesca
F
Meneghello
Centre for Computational Imaging & Simulation Technologies in Biomedicine (CISTIB), Department of Electronic and Electrical Engineering, University of Sheffield, Sheffield. United Kingdom.
Susheel
S
Varma
Centre for Computational Imaging & Simulation Technologies in Biomedicine (CISTIB), Department of Electronic and Electrical Engineering, University of Sheffield, Sheffield. United Kingdom.
Alejandro F
AF
Frangi
Department of Neuroscience - Medical School, University of Sheffield, Beech Hill Road, Royal Hallamshire Hospital, N floor, room N130, Sheffield, S10 2RX. United Kingdom.
Annalena
A
Venneri
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D053327:Apolipoprotein E4 / Q000235:genetics*; D001931:Brain Mapping; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D000073216:Mental Status and Dementia Tests; D009415:Nerve Net; D016571:Neural Networks, Computer; D009434:Neural Pathways / Q000000981:diagnostic imaging; D009483:Neuropsychological Tests
D053327:Apolipoprotein E4
Functional connectivity; disinhibition hypothesis; hippocampus; Alzheimer's disease; network
disruption; posterior cingulate