APR isoforms in platelets: A peripheral marker of alzheimer disease related to the disease severity

Platelets represent an important peripheral source of Amyloid Precursor Protein (APP). Three major APP isoforms with apparent molecular weight (MW) in the range of 100130 kDa are present in membranes of platelets. To investigate whether changes in platelets APP isoforms are specifically related to Alzheimer Disease (AD), the level of APP isoforms was evaluated in platelets obtained from 27 AD patients (12 mild, 8 moderate, 9 severe), from 16 agematched patients affected by non-Alzheimer dementing disorders (NADD), and from 15 age-matched controls (NC). Platelets were prepared from 30 ml of blood and subjected to Western Blot analysis using monoclonal antibody (22C11). The ratio between the immunoreactivity of the higher M W APP isoform (130kDa) and the lowest isoforms (100-110 kDa) was calculated. This value was significantly lower in AD patients compared with both NC and NADD patients (p<001 vs control and non-AD patients). When AD patients were grouped according to CDR scores, a strong association was found between severity of dementia and platelets' APP isoform ratio (mild AD=0.48±0.14; moderate AD=0.33±0.15; severe AD=0.25±0.08). Together these findings show that an altered ratio between the three major APP isoforms in platelets might represent a peripheral marker of AD and a sensitive measure of the progression of the disease.