• Catherine F Slattery, Jiaying Zhang, Ross W Paterson, Alexander J M Foulkes, Amelia Carton, Kirsty Macpherson, Laura Mancini, David L Thomas, Marc Modat, Nicolas Toussaint, David M Cash, John S Thornton, Susie M D Henley, Sebastian J Crutch, Daniel C Alexander, Sebastien Ourselin, Nick C Fox, Hui Zhang, and Jonathan M Schott.
• Department of Neurodegenerative Disease, Institute of Neurology, UCL, London, UK. Electronic address: c.slattery@ucl.ac.uk.
• Neurobiol. Aging. 2017 Sep 1; 57: 8-17.

AbstractMechanisms underlying phenotypic heterogeneity in young onset Alzheimer disease (YOAD) are poorly understood. We used diffusion tensor imaging and neurite orientation dispersion and density imaging (NODDI) with tract-based spatial statistics to investigate apolipoprotein (APOE) ε4 modulation of white-matter damage in 37 patients with YOAD (22, 59% APOE ε4 positive) and 23 age-matched controls. Correlation between neurite density index (NDI) and neuropsychological performance was assessed in 4 white-matter regions of interest. White-matter disruption was more widespread in ε4+ individuals but more focal (posterior predominant) in the absence of an ε4 allele. NODDI metrics indicate fractional anisotropy changes are underpinned by combinations of axonal loss and morphological change. Regional NDI in parieto-occipital white matter correlated with visual object and spatial perception battery performance (right and left, both p = 0.02), and performance (nonverbal) intelligence (WASI matrices, right, p = 0.04). NODDI provides tissue-specific microstructural metrics of white-matter tract damage in YOAD, including NDI which correlates with focal cognitive deficits, and APOEε4 status is associated with different patterns of white-matter neurodegeneration.Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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