TY - JOUR
T1 - Decreased platelet APP isoform ratios in autosomal dominant Alzheimer’s disease
T2 - Baseline data from a DIAN cohort subset
AU - Dominantly Inherited Alzheimer Network
AU - Chatterjee, Pratishtha
AU - Gupta, Veer B.
AU - Fagan, Anne M.
AU - Jasielec, Mateusz S.
AU - Xiong, Chengjie
AU - Sohrabi, Hamid R.
AU - Dhaliwal, Satvinder
AU - Taddei, Kevin
AU - Bourgeat, Pierrick
AU - Brown, Belinda M.
AU - Benzinger, Tammie
AU - Bateman, Randall J.
AU - Morris, John C.
AU - Martins, Ralph N.
N1 - Publisher Copyright:
© 2015 Bentham Science Publishers.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Amyloid precursor protein
KW - Biomarkers
KW - Neuropsychological tests
KW - Pittsburgh compound B
KW - Platelets
UR - http://www.scopus.com/inward/record.url?scp=84989227764&partnerID=8YFLogxK
U2 - 10.2174/1567205012666150204125732
DO - 10.2174/1567205012666150204125732
M3 - Article
C2 - 25654503
AN - SCOPUS:84989227764
SN - 1567-2050
VL - 12
SP - 157
EP - 164
JO - Current Alzheimer Research
JF - Current Alzheimer Research
IS - 2
ER -