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

Abstract

Platelets carry over 95% of the circulating Alzheimer's β-amyloid precursor protein (AβPP), and release soluble and hydrophobic proteolytic fragments of AβPP 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 AβPP 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 AβPP), while the AβPP processing defect and consequent AβPP retention on the membrane is absent and is thus likely to be AD-specific. The hyperacidiftcation defect correlates with all three dementias and with the presence of apolipoprotein E4 which has been implicated as a risk factorial-AD.