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Platelet Amyloid Precursor Protein ratio of different abnormal forms and 99mTc–ECD SPECT perfusion analysis were evaluated in Mild Cognitive Impairment (MCI) subjects who progressed to Alzheimer Disease (AD) and in stable MCI. We report that their combined evaluation increases the discriminative power of the analysis in identifying presymptomatic AD. The positive predictive value of these combined markers in identifying progressive MCI was 0.87, and the negative predictive value was 0.90. This observation suggests that the interplay of different markers should be considered for enhancing diagnostic accuracy of pre–clinical AD. [ABSTRACT FROM AUTHOR]

Previous findings demonstrated an altered pattern of amyloid precursor protein (APP) forms in platelets of Alzheimer disease (AD) patients, compared both with healthy control subjects or patients with non-Alzheimer-type dementia. The present study aims to evaluate whether platelet APP form ratio (APPr) is altered in patients with early stage AD. We selected 40 patients with early stage AD and 40 age-matched healthy controls. Compared with controls (mean±SD=0.91±0.3), mean APPr was decreased in AD (mean±SD=0.46±0.26, p<0.0001). Sixteen very mild AD patients (clinical dementia rating=0.5), identified among the AD group, showed a significant decrease of APPr values (mean±SD=0.50±0.3, p<0.0001). These findings indicate that alteration of APP processing in platelets is an early event and suggest that this assay might be of diagnostic value in differentiating mild AD from normal ageing. [ABSTRACT FROM AUTHOR]

Abstract We have tested whether different agonists of metabotropic glutamate receptors could induce translocation of selective protein kinase C isozymes in nerve terminals. In rat cortical synaptosomes 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD; 100 μm) induced an increase in translocation to 124.6 ± 5.7% of basal unstimulated conditions of the Ca++-independent protein kinase Cε, but not of the Ca++-dependent isozyme β. This effect was counteracted by 1-aminoindan-1,5-dicarboxylic acid (100 μm), an antagonist of metabotropic glutamate receptor 1. On the other hand, (+)-α-methyl-4-carboxyphenylglycine [(+)-MCPG], an antagonist of metabotropic glutamate receptors group I and II, did not antagonize the effect of 1S,3R-ACPD, and per se induced a translocation of protein kinase Cε of 164 ± 17.7% of basal unstimulated conditions. Because the (+)-MCPG induction of protein kinase Cε translocation was not antagonized by 1-aminoindan-1,5-dicarboxylic acid, it is suggested that 1S,3R-ACPD and (+)-MCPG activate this signal transduction pathway through distinct membrane receptors. Indeed (2-[2′′-carboxy-3′-phenylcyclopropyl]glycine)-13 (300 nm), a new compound known to antagonize metabotropic glutamate receptors coupled to phospholipase D, was able to antagonize protein kinase Cε translocation induced by (+)-MCPG. Moreover (+)-MCPG directly induced phospholipase D activity, measured as [3H]phosphoethanol production in cortical synaptosomes. These data suggest that in cortical nerve terminals (i) distinct metabotropic glutamate receptors, coupled to different signal transduction pathways, are present, (ii) (+)-MCPG is able to induce protein kinase Cε translocation, and that (iii) a metabotropic glutamate receptor associated to phospholipase D might influence translocation of protein kinase C in a calcium-independent manner. [ABSTRACT FROM AUTHOR]