Platelets from patients with Alzheimer's disease or other dementias exhibit disease-specific and apolipoprotein E correlatable defects

Platelets carry over 95% of the circulating Alzheimer's beta-amyloid precursor protein (A beta PP), and release soluble and hydrophobic proteolytic fragments of A beta PP upon activation. These cells may be the source of cerebrovascular amyloid peptides, a part of Alzheimer's disease (AD) pathology. Our previous studies showed that platelets from patients with advanced AD exhibit both signal transduction (hyperacidification) and A beta PP processing defects. Here, we show further that a similar hyperacidification also exists in patients with Pick's disease (a dementia with AD-like symptoms but a different amyloid pathology) or Down syndrome (trisomy and hence overproduction of A beta PP), while the A beta PP processing defect and consequent A beta PP retention on the membrane is absent and is thus likely to he AD-specific. The hyperacidification defect correlates with all three dementias and with the presence of apolipoprotein E4 which has been implicated as a risk factor for AD.