The Effects of Gene Mutations on Default Mode Network in Familial Alzheimer’s Disease
| Autor: | Ove Almkvist, Anne Kinhult Ståhlbom, Lars-Olof Wahlund, Caroline Graff, Xiaozhen Li, Steinunn Thordardottir, Eric Westman, Kaj Blennow |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Amyloid Models Neurological Tau protein tau Proteins Neuropsychological Tests Gene mutation behavioral disciplines and activities Functional Laterality Amyloid beta-Protein Precursor 03 medical and health sciences Apolipoproteins E 0302 clinical medicine Cerebrospinal fluid Neuroimaging Alzheimer Disease Neural Pathways mental disorders Image Processing Computer-Assisted Presenilin-1 medicine Humans Dementia Default mode network Family Health Amyloid beta-Peptides Resting state fMRI biology General Neuroscience Brain General Medicine Middle Aged medicine.disease Magnetic Resonance Imaging Peptide Fragments humanities Psychiatry and Mental health Clinical Psychology 030104 developmental biology Mutation biology.protein Female Geriatrics and Gerontology Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's Disease. 56:327-334 |
| ISSN: | 1875-8908 1387-2877 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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