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,
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