Abstract
Background: Whether the presence of the Apolipoprotein E ε4 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 ε4 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: 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. 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 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.
| Original language | English |
|---|---|
| Pages (from-to) | 766-777 |
| Number of pages | 12 |
| Journal | Current Alzheimer Research |
| Volume | 14 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jan 1 2017 |
Fingerprint
Keywords
- Alzheimer’s disease
- Disinhibition hypothesis
- Functional connectivity
- Hippocampus
- Network disruption
- Posterior cingulate
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
Cite this
ApoE ε4 allele related alterations in hippocampal connectivity in Early Alzheimer’s disease support memory performance. / de Marco, Matteo; Vallelunga, Annamaria; Meneghello, Francesca; Varma, Susheel; Frangi, Alejandro F.; Venneri, Annalena; Alzheimer's Disease Neuroimaging Initiative.
In: Current Alzheimer Research, Vol. 14, No. 7, 01.01.2017, p. 766-777.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - ApoE ε4 allele related alterations in hippocampal connectivity in Early Alzheimer’s disease support memory performance
AU - de Marco, Matteo
AU - Vallelunga, Annamaria
AU - Meneghello, Francesca
AU - Varma, Susheel
AU - Frangi, Alejandro F.
AU - Venneri, Annalena
AU - Alzheimer's Disease Neuroimaging Initiative
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Background: Whether the presence of the Apolipoprotein E ε4 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 ε4 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: 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. 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 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.
AB - Background: Whether the presence of the Apolipoprotein E ε4 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 ε4 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: 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. 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 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.
KW - Alzheimer’s disease
KW - Disinhibition hypothesis
KW - Functional connectivity
KW - Hippocampus
KW - Network disruption
KW - Posterior cingulate
UR - http://www.scopus.com/inward/record.url?scp=85025087460&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85025087460&partnerID=8YFLogxK
U2 - 10.2174/1567205014666170206113528
DO - 10.2174/1567205014666170206113528
M3 - Article
VL - 14
SP - 766
EP - 777
JO - Current Alzheimer Research
JF - Current Alzheimer Research
SN - 1567-2050
IS - 7
ER -