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The Effects of Gene Mutations on Default Mode Network in Familial Alzheimer’s Disease
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2017 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 56, no 1, p. 327-334Article in journal (Refereed) Published
Abstract [en]

Familial Alzheimer’s disease (FAD) mutations have very high penetrance but age at onset and rate of disease progression differ. Neuroimaging and cerebrospinal fluid (CSF) examinations in mutation carriers (MCs) may provide an opportunity to identify early biomarkers that can be used to track disease progression from presymptomatic to the dementia stages of disease. The default mode network (DMN) is a resting state neuronal network composed of regions known to associate with amyloid deposition in AD. We hypothesized that functional connectivity in the DMN might change at pre-clinical stages in FAD MCs and correlate with changes in CSF biomarkers as a consequence of AD brain pathology. To test the hypothesis, we compared the functional connectivity in DMN between pre-MCs/MCs and non-carriers (NCs). No significant differences between pre-MCs and NCs were observed. When comparing all MCs with NCs, significant decreased functional connectivity in the right inferior parietal lobule, right precuneus, and left posterior cingulate cortex were found. We also found statistically significant correlations between CSF amyloid-β 42 and tau protein levels and average Z-score, a resting-state functional MRI measurement reflecting the degree of the correlation between a given voxel’s time courses and the time courses corresponding to DMN, from the region with statistical difference. The observed disruption of DMN and pathological levels of AD CSF-biomarkers in FAD MCs are similar to the changes described in sporadic AD, which give further support that amyloid and tau pathology impairs neuronal and synaptic function.

Place, publisher, year, edition, pages
2017. Vol. 56, no 1, p. 327-334
Keywords [en]
cerebrospinal fluid biomarkers, default mode network, familial Alzheimer’s disease, mutation carrier, resting-state functional MRI, synaptic function
National Category
Psychology Geriatrics
Research subject
Psychology
Identifiers
URN: urn:nbn:se:su:diva-137930DOI: 10.3233/JAD-160730ISI: 000393886100027OAI: oai:DiVA.org:su-137930DiVA, id: diva2:1065169
Available from: 2017-01-13 Created: 2017-01-13 Last updated: 2017-11-29Bibliographically approved

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