Decreased platelet APP isoform ratios in autosomal dominant Alzheimer's disease

baseline data from a DIAN Cohort subset

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, Ralph N. Martins*, Dominantly Inherited Alzheimer Network

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)157-164
Number of pages8
JournalCurrent Alzheimer Research
Volume12
Issue number2
DOIs
Publication statusPublished - 1 May 2015
Externally publishedYes

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