Decreased platelet APP isoform ratios in autosomal dominant Alzheimer's disease: baseline data from a DIAN cohort subset

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 differenc...

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Main Authors: Chatterjee, P., Gupta, V., Fagan, A., Jasielec, M., Xiong, C., Sohrabi, H., Dhaliwal, Satvinder, Taddei, K., Bourgeat, P., Brown, B., Benzinger, T., Bateman, R., Morris, J., Martins, R.
Format: Journal Article
Published: BENTHAM SCIENCE PUBL LTD 2015
Online Access:http://hdl.handle.net/20.500.11937/13119
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author Chatterjee, P.
Gupta, V.
Fagan, A.
Jasielec, M.
Xiong, C.
Sohrabi, H.
Dhaliwal, Satvinder
Taddei, K.
Bourgeat, P.
Brown, B.
Benzinger, T.
Bateman, R.
Morris, J.
Martins, R.
author_facet Chatterjee, P.
Gupta, V.
Fagan, A.
Jasielec, M.
Xiong, C.
Sohrabi, H.
Dhaliwal, Satvinder
Taddei, K.
Bourgeat, P.
Brown, B.
Benzinger, T.
Bateman, R.
Morris, J.
Martins, R.
author_sort Chatterjee, P.
building Curtin Institutional Repository
collection Online Access
description 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.
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spelling curtin-20.500.11937-131192017-01-30T11:34:56Z Decreased platelet APP isoform ratios in autosomal dominant Alzheimer's disease: baseline data from a DIAN cohort subset Chatterjee, P. Gupta, V. Fagan, A. Jasielec, M. Xiong, C. Sohrabi, H. Dhaliwal, Satvinder Taddei, K. Bourgeat, P. Brown, B. Benzinger, T. Bateman, R. Morris, J. Martins, R. 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. 2015 Journal Article http://hdl.handle.net/20.500.11937/13119 BENTHAM SCIENCE PUBL LTD restricted
spellingShingle Chatterjee, P.
Gupta, V.
Fagan, A.
Jasielec, M.
Xiong, C.
Sohrabi, H.
Dhaliwal, Satvinder
Taddei, K.
Bourgeat, P.
Brown, B.
Benzinger, T.
Bateman, R.
Morris, J.
Martins, R.
Decreased platelet APP isoform ratios in autosomal dominant Alzheimer's disease: baseline data from a DIAN cohort subset
title Decreased platelet APP isoform ratios in autosomal dominant Alzheimer's disease: baseline data from a DIAN cohort subset
title_full Decreased platelet APP isoform ratios in autosomal dominant Alzheimer's disease: baseline data from a DIAN cohort subset
title_fullStr Decreased platelet APP isoform ratios in autosomal dominant Alzheimer's disease: baseline data from a DIAN cohort subset
title_full_unstemmed Decreased platelet APP isoform ratios in autosomal dominant Alzheimer's disease: baseline data from a DIAN cohort subset
title_short Decreased platelet APP isoform ratios in autosomal dominant Alzheimer's disease: baseline data from a DIAN cohort subset
title_sort decreased platelet app isoform ratios in autosomal dominant alzheimer's disease: baseline data from a dian cohort subset
url http://hdl.handle.net/20.500.11937/13119