Platelets as a peripheral district where to study pathogenetic mechanisms of Alzheimer disease: the case of amyloid precursor protein

Alzheimer disease is a progressive neurodegenerative disease, characterised by a progressive cognitive and memory decline. From a neuropathological po int of view, Alzheimer disease is defined by the presence of characteristic lesions, i.e. mature senile plaques, neurofibrillary tangles (NFTs) and am yloid angiopathy. In particular, accumulation of the amyloid beta-peptide i n the brain parenchyma and vasculature is an invariant event in the pathoge nesis of both sporadic and familial Alzheimer cases. Amyloid beta-peptide o riginates from a larger precursor, the amyloid precursor protein (APP) ubiq uitously expressed. Among the different peripheral cells expressing APP for ms, platelets are particularly interesting since they show concentrations o f its isoforms equivalent to those found in brain. Moreover, a number of la boratories independently described alterations in APP metabolism/concentrat ion in platelets of Alzheimer patients when compared to control subjects ma tched for demographic characteristics. These observations defined the frame of our work aimed to investigate if a correlation between levels of platel et APP forms and Alzheimer disease could be detected. We have reported that patients affected by Alzheimer disease show a differential level of platel et APP forms. This observation has several implications: APP processing abn ormalities, believed to be a very early change in Alzheimer disease in neur onal compartment, do occur in extraneuronal tissues, such as platelets, thu s, suggesting that Alzheimer disease is a systemic disorder; further, our d ata strongly indicate that a differential level of platelet APP isoforms ca n be considered a potential peripheral marker of Alzheimer disease allowing for discrimination between Alzheimer and other types of dementia. (C) 2000 Elsevier Science B.V. All rights reserved.