This trans lates to a FDR of 6. 9%. The list of 144 significantly changed proteins corresponding to selleck chemical Calcitriol this FDR in AD relative to the control platelet membrane fraction is given in Table S3 in Additional file 1. Changes in platelet secretion and activation observed in patients with AD Ontologies significantly overrepresented within the list of 144 significantly changing proteins were determined using DAVID. Fifteen proteins, or about 10% of the list, represent factors likely specific to plate lets that fall into the following six overlapping categories, platelet activation, pla telet alpha granules, secretory granules, the complement control module, complement and coagulation cascades, and pla telet alpha granule lumen.

All but one of the proteins in these six categories were sig nificantly decreased, rather than increased, in AD rela tive to the control pool, including a, b, and g chains of fibrinogen. Fibrinogen is involved in the coagulation Inhibitors,Modulators,Libraries cascade and is secreted by alpha granules after platelet activation. It has also been included in several panels of biomarkers for AD. According to Thambisetty et al. decreased fibrinogen in association with other changes in plasma has been associated with lower brain volumes in AD. Craig Shapiro et al. have included fibrino gen in a multiplex immunoassay panel to analyze CSF biomarkers for AD. They reported that a finding of increased fibrinogen levels in the CSF in association with changes in other proteins increases the ability of the CSF tau Ab42 ratio to discriminate between patients with very mild to mild dementia and those who are cog nitively normal.

Platelets release alpha granules when activated. As this study looked at a membrane enriched fraction, this finding suggests that AD platelets have a generally decreased or exhausted reserve of alpha Inhibitors,Modulators,Libraries granules consistent with having undergone activation. We speculate that low levels of fibrinogen observed in platelets from patients with AD is complementary to the reported increase in fibrinogen infiltration into AD cen tral nervous system tissue associated with Ab depositions and microglial activation. Inhibitors,Modulators,Libraries Contact of pla telets with amyloid aggregates has been shown to result in their activation, and Ab stimulates abnormal clots of cleaved fibrinogen resistant to clearance.

These findings in combination suggest Inhibitors,Modulators,Libraries widespread AD specific platelet activation, Inhibitors,Modulators,Libraries supported by previous studies that have following website reported platelet activation in individuals with AD. The single increasing protein in Table 2, platelet glyco protein IX, a surface protein on platelet and alpha granule membranes is known to act as a receptor for von Willebrand factor. This represents a novel plate let surface expressed candidate marker that could be spe cifically increasing in a manner linked to AD.