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Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Decreased Platelet APP Isoform Ratios in Autosomal Dominant Alzheimer’s Disease: Baseline Data from a DIAN Cohort Subset

Author(s): Pratishtha Chatterjee, Veer B. Gupta, Anne M. Fagan, Mateusz S. Jasielec, Chengjie Xiong, Hamid R. Sohrabi, Satvinder Dhaliwal, Kevin Taddei, Pierrick Bourgeat, Belinda M. Brown, Tammie Benzinger, Randall J. Bateman, John C. Morris and Ralph N. Martins

Volume 12 , Issue 2 , 2015

Page: [157 - 164] Pages: 8

DOI: 10.2174/1567205012666150204125732

Price: $65

Abstract

Introduction: This study examines platelet amyloid precursor protein (APP) isoform ratios of 120KDa to 110KDa (APPr) between mutation carriers (MC) carrying a mutation for autosomal dominant Alzheimer’s disease (ADAD) and non-carriers (NC). Two previous studies reported no significant difference in APPr between ADAD MC and NC, which may have been due to the small sample size in both studies. The current study examines APPr in MC versus NC in a larger sample. In addition, it investigated whether APPr correlate with neuroimaging data, neuropsychological data and cerebrospinal fluid biomarkers in a cohort subset derived from the Dominantly Inherited Alzheimer Network (DIAN) study. Methods: APPr were quantified by western blotting. Fifteen MC (symptomatic and asymptomatic) were compared against twelve NC using univariate general linear model. All participants underwent neuroimaging and neuropsychological testing which were correlated with APPr using Pearson’s correlation coefficient (r). Results: APPr were lower in MC compared to NC (p=0.003) while Mini-Mental State Examination (MMSE) scores were not significantly different (p>0.1). Furthermore, APPr inversely correlated with amyloid imaging in the Caudate Nucleus (r=-0.505; p<0.05) and Precuneus (r=-0.510; p<0.05). Conclusion: APPr are lower in ADAD MC compared to NC, and inversely correlated with brain amyloid load prior to significant differences in cognitive health. However, the use of APPr as a biomarker needs to be explored further.

Keywords: Alzheimer’s disease, amyloid precursor protein, biomarkers, neuropsychological tests, Pittsburgh compound B, platelets.


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