Bu��e et al. found that THBS1 stained senile plaques in AD brains and suggested it may be involved in plaque formation. Recently, Horn et al. examined next the effect of human neutrophil alpha defensins, components of the innate immune system, on platelet activation. They found that these defensins activated pla telets and led to fibrinogen and THBS1 binding. More over, these fibrinogen and THBS1 complexes formed amyloid like structures. Such a cascade could also play a role in AD pathogenesis. Other significantly changed amyloidogenesis associated proteins identified in the platelet membrane proteome included increased beta 2 microglobulin 1. 21 and decreased gelsolin 1. 40. Increased B2M binding to the surface of blood cells including granulocytes, lymphocytes and monocytes is characteristic of chronic hemodialysis, and co occurs with vascular and renal amyloid deposits of this protein.

Notably, none of the patients involved in this analysis had end stage renal disease or required dialysis. Consistent with a specific effect of AD on this protein, elevated B2M was reported as one of eight CSF biomarkers, which together made up a Inhibitors,Modulators,Libraries multianalyte profile that was able to distinguish both probable AD and Parkinsons disease individuals from controls. Earlier, high B2M in prob able AD patient CSF was also found via a proteomic approach. Gelsolin is a chaperone with multiple functions that has been shown to bind to Ab and ApoE and has an independent involvement in certain amyloidoses.

Although it is reportedly unchanging in Inhibitors,Modulators,Libraries AD brain, it was previously identified as a plasma AD marker that correlated positively with rapidity of cognitive decline in clinically diagnosed AD patients. However, by itself, a decrease in plasma gelsolin is also associated with multiple morbidities includ ing oxygen imbalances, major trauma, malaria, and liver injury. Thus, although the changes we describe for amyloidogenic proteins including THBS1, B2M, and gelso lin Inhibitors,Modulators,Libraries in the platelet membrane proteome in AD are consis tent with what is known to occur in individuals diagnosed with AD, it is also apparent that alone, these protein changes are not markers with adequate specificity for AD obviating their inclusion into broader multianalyte profiles that consider a panel of changing proteins, be it on the membranes of platelets, or in CSF.

Co occurrence Inhibitors,Modulators,Libraries of other pooled analyte changes consistent with previous biomarker studies Beyond the above potential markers for clinically diag nosed AD, which confirm platelet activation plus a change in each of three Inhibitors,Modulators,Libraries amyloidosis linked proteins THBS1, B2M, and gelsolin, we asked what other changes found are consistent with previously Navitoclax ABT-263 pro posed AD markers or potentially linked to proteins involved in disease mechanism, albeit not necessarily through activity in platelets.