Investigating amyloid precursor protein and tau in human platelets as potential blood biomarkers in individuals at risk of Alzheimer's disease

While detecting neocortical amyloid-beta (NAL) by positron emission tomography (PET) offers a unique opportunity to recognise individuals at potential risk of Alzheimer's disease (AD), its uneconomical and invasive nature calls for a more accessible and cost-effective biomarker for greater clinical utility. Platelets are rich with Amyloid Precursor Protein (APP), the parent protein for amyloid-beta, with literature reporting significant alterations in platelet APP isoform ratio (APPr), APP processing secretases ADAM10 (a disintegrin and metalloproteinase) and BACE1 (beta-secretase 1), and tau in AD compared to normal individuals. Therefore, this study aims to explore whether these platelet proteins of interest are associated with NAL prior to cognitive impairment and, assess its diagnostic accuracy for individuals at risk of AD. 30 cognitively normal individuals thought to be at risk of AD and 30 cognitively normal individuals at no apparent risk to AD, were selected for the study. Platelets collected from peripheral blood were evaluated with western blot for the interested proteins, and statistical associations were assessed between NAL participants and, with cognitive performance. The APP mature isoform and the ratio of high molecular weight/low molecular weight (HMW/LMW) tau were significantly associated with NAL, while the HMW/LMW tau ratio was significantly inversely correlated with cognitive performance. The accuracy of prediction for distinguishing NAL participants was increased (accuracy = 80%) when the APP mature isoform and HMW/LMW tau ratio were added to the base model of age, gender and APOE e4 allele status. The nature of these associations will expand the current knowledge on platelet-related alterations in individuals at risk of AD. Furthermore, future investigations may enhance the understanding of platelet proteins as potential diagnostic and prognostic biomarkers for early AD prior to cognitive decline -- abstract.