title: The Effects of Gene Mutations on Default Mode Network in Familial Alzheimer's Disease.
abstract: 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.
authors.affiliation: Department of Radiology, Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine, Beijing, China.|Division of Clinical Geriatrics, Center for Alzheimer Disease Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden.
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of Clinical Geriatrics, Center for Alzheimer Disease Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden.
authors.forename: Eric
authors.initials: E
authors.lastname: Westman
authors.affiliation: Division of Neurogeriatrics, Center for Alzheimer Disease Research, Department of NVS, Karolinska nstitutet, Huddinge, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Huddinge, Sweden.
authors.forename: Steinunn
authors.initials: S
authors.lastname: Thordardottir
authors.affiliation: Division of Neurogeriatrics, Center for Alzheimer Disease Research, Department of NVS, Karolinska nstitutet, Huddinge, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Huddinge, Sweden.
authors.forename: Anne Kinhult
authors.initials: AK
authors.lastname: Ståhlbom
authors.affiliation: Division of Clinical Geriatrics, Center for Alzheimer Disease Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden.|Department of Psychology, Stockholm University, Stockholm, Sweden.
authors.forename: Ove
authors.initials: O
authors.lastname: Almkvist
authors.affiliation: Clinical Neurochemistry Lab, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Division of Clinical Geriatrics, Center for Alzheimer Disease Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden.
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
authors.affiliation: Division of Neurogeriatrics, Center for Alzheimer Disease Research, Department of NVS, Karolinska nstitutet, Huddinge, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Huddinge, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Graff
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging*; D005192:Family Health; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009154:Mutation / Q000235:genetics*; D009434:Neural Pathways / Q000000981:diagnostic imaging; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D053764:Presenilin-1 / Q000235:genetics; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Cerebrospinal fluid biomarkers; default mode network; familial Alzheimer’s disease; mutation carrier; resting-state functional MRI; synaptic function