PLATELETS FROM PATIENTS WITH ALZHEIMERS-DISEASE OR OTHER DEMENTIAS EXHIBIT DISEASE-SPECIFIC AND APOLIPOPROTEIN-E CORRELATABLE DEFECTS

Platelets carry over 95% of the circulating Alzheimer's beta-amyloid p recursor protein (A beta PP), and release soluble and hydrophobic prot eolytic fragments of A beta PP upon activation. These cells may be the source of cerebrovascular amyloid peptides, a part of Alzheimer's dis ease (AD) pathology. Our previous studies showed that platelets from p atients with advanced AD exhibit both signal transduction (hyperacidif ication) and A beta PP processing defects. Here, we show further that a similar hyperacidification also exists in patients with Pick's disea se (a dementia with AD-like symptoms but a different amyloid pathology ) or Down syndrome (trisomy and hence overproduction of A beta PP), wh ile 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 h yperacidification defect correlates with all three dementias and with the presence of apolipoprotein E4 which has been implicated as a risk factor for AD.