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Title: Divergent network patterns of amyloid-β deposition in logopenic and amnestic Alzheimer’s disease presentations
Austin Authors: Leyton, Cristian E;Cassidy, Ben;Villemagne, Victor L ;Jones, Gareth;Kwok, John B;Rowe, Christopher C ;Ballard, Kirrie J;Piguet, Olivier;Hodges, John R
Affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia
Faculty of Health Sciences, The University of Sydney, Lidcombe
Neuroscience Research Australia Randwick
Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, New South Wales, Australia
Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria
School of Medical Sciences, The University of New South Wales, Sydney, New South Wales, Australia
Issue Date: 21-Oct-2015
Publication information: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 2016; 1(1): 24-31
Abstract: Background Despite divergent clinical features, language and amnestic presentations of Alzheimer’s disease (AD) appear to show comparable regional amyloid-β (Aβ) burden. By using a statistical network approach, we aimed to identify complex network patterns of Aβ deposition and explore the effect of apolipoprotein E (APOE) ε4 allele on cortical Aβ burden across AD phenotypes. Methods Sixteen amnestic AD participants and 18 cases with logopenic-variant of primary progressive aphasia (lv-PPA) with a high cortical Aβ burden were selected. A comprehensive clinical assessment, Aβ imaging, and APOE genotyping were performed in all cases. Statistical network analysis was undertaken based on the estimation of sparse partial correlations of Aβ burden between cortical regions. Global and regional network statistical parameters as well as the effect of APOE ε4 genotype on cortical Aβ were explored. Results The two groups showed equivalent distribution of cortical amyloid burden and frequency of APOE ε4 genotype. Statistical network analysis, however, demonstrated divergent connectivity properties. The lv-PPA group demonstrated higher mean network degree and shorter characteristic path length than the amnestic AD group. Amnestic AD cases showed connectivity hubs confined to the mesial temporal and prefrontal lobes bilaterally, whereas lv-PPA cases showed hubs scattered across the whole cortical mantle. An interaction effect on total Aβ burden between APOE genotype and AD presentations was also detected. Conclusions The network analysis reveals interregional network differences not evident using a simple comparison of Aβ burden. This suggests that regional neurotoxic effects may explain the phenotypical differences in AD presentation and that these can be modulated by APOE genotype.
DOI: 10.1016/j.bpsc.2015.09.004
ORCID: 0000-0003-3910-2453
Journal: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Type: Journal Article
Subjects: Alzheimer’s disease
Apolipoprotein E ε4
Complex network analysis
Logopenic variant of primary progressive aphasia
Pittsburgh Compound B positron emission tomography (PiB-PET)
Appears in Collections:Journal articles

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