ApoE influences regional white-matter axonal density loss in Alzheimer%26apos;s disease

作者：Slattery Catherine F; Zhang Jiaying; Paterson Ross W; Foulkes Alexander J M; Carton Amelia; Macpherson Kirsty; Mancini Laura; Thomas David L; Modat Marc; Toussaint Nicolas; Cash David M; Thornton John S; Henley Susie M D; Crutch Sebastian J; Alexander Daniel C; Ourselin Sebastien; Fox Nick C; Zhang Hui; Schott Jonathan M

来源：Neurobiology of Aging, 2017, 57: 8-17.

DOI：10.1016/j.neurobiolaging.2017.04.021

• Alzheimer's disease
• Diffusion tensor imaging
• Neurite orientation dispersion and density
• imaging
• Apoe
• White matter
• Phenotype

Mechanisms 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) epsilon 4 modulation of white-matter damage in 37 patients with YOAD (22, 59% APOE e4 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 epsilon 4+ individuals but more focal (posterior predominant) in the absence of an e4 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 APOE epsilon 4 status is associated with different patterns of white-matter neurodegeneration.

• 出版日期2017-9