WHITE MATTER MICROSTRUCTURE AND AMYLOID AGGREGATION IN COGNITIVELY HEALTHY, ELDERLY IDENTICAL TWINS

Abstract

Background: Lack of effective predictive models and/or treatments for Alzheimer's Disease (AD) has led a growing movement towards better characterization of pre-clinical stages. One currently established biomarker is positron emission tomography (PET) measured amyloid beta load. Here, in a genetically informative population of cognitively healthy, elderly identical twins, we compared this biomarker to a promising new candidate; white matter (WM) integrity measured by diffusion tensor imaging (DTI). Method(s): Eighty-eight genetically identical twin-pairs and 14 individual twins (n=190, mean age(SD)= 70 (7.5)) were selected from the EMIF-AD PreclinAD study. Abeta load, as a measure for amyloid aggregation, was quantified from [18F] Flutemetamol PET scans. Regional measurements of fractional anisotropy (FA) and mean diffusivity (MD), obtained with tract-based spatial statistics (TBSS) from FMRIB's Software Library (FSL), were used as measures for WM integrity. Within-subject associations between amyloid aggregation and WM integrity were estimated using generalized estimating equations, correcting for twin dependency. A possible shared etiology between amyloid aggregation and WM integrity was further explored using a cross-twin cross-trait (CTCT) design, testing whether amyloid aggregation in a twin could predict WM integrity in the co-twin. Analyses were adjusted for age, sex and intracranial volume. Result(s): Amyloid aggregation predicted trends in increased FA and decreased MD. Regions of interest (ROIs) that met p