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

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.

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Platelet Dynamics in Neurodegenerative Disorders: Investigating the Role of Platelets in Neurological Pathology

“…Such assays contribute to the ongoing efforts in developing diagnostic tools and markers that can aid in the early detection and differentiation of neurodegenerative disorders. Evidence suggests that altered APP processing occurs before clinical manifestations in AD patients with mutations associated with the autosomal dominant form of the disease [72]. This observation highlights the potential of APP isoforms in PLTs as surrogate biomarkers for assessing disease progression and treatment effectiveness.…”