MP in Neuroinflammation: Findings from the Authors' Group Introduction

This article explains how the authors became involved in studies of neuroinflammatory conditions. Although some of the references are now old, the findings of section “MP in Vascular Dementia” are not widely appreciated and may be important to future work.

MP in Vascular Dementia

It was observed by Y.S. Ahn that patients with immune thrombocytopenia (ITP) were protected against bleeding symptoms by high levels of circulating platelet MP [27], later extended to include red cell-derived MP (RMP). Furthermore, he observed that a number of patients with long-term chronic elevation of PMP exhibited slowly progressing cognitive decline, which in some cases progressed to dementia. Imaging with MRI showed periventricular and subcortical white matter hyperintensities consistent with ischemic small-vessel disease. We suggested that antiplatelet antibodies activate platelets to enhance shedding of procoagulant PMP, promoting thrombotic occlusions of small vessels. In a follow-up study, it was observed that cognitive impairment progressed more rapidly in splenectomized patients [28]. This further supports a causative link of PMP with cognitive impairment since splenectomy retards clearance of PMP [29]. Of note, patients with cognitive impairment had significantly higher platelet-associated IgM (but not IgG) compared to patient controls (p < 0.02) [28].

A related study found that the association between PMP and cognitive decline was not limited to ITP patients [30]. Alzheimer’s disease (AD) was ruled out. Recent work from other laboratories tends to confirm the main findings mentioned above [31]. Recent proteomic study of MP in patients with lacunar infarcts suggests MP assay as a diagnostic aid and for insight into the disease process [32].

Also of related interest was a study of the electrophoretic mobility of patient platelets in which it was observed that the patients with cognitive impairments had the highest mobility [33]. It was not possible at that time to measure zeta potentials of the MP but it is expected that MP will have electric charge related to that of the parent cell. This leads us to conjecture that high negative charge on MP could predispose to vascular dementia. Others have shown that electric charge can be crucial to the functional properties of MP [34]. These observations may bear on postoperative cognitive impairment, since surgical procedures entail extensive disruption of endothelia and activation of platelets and other cells, inducing release of MP [35, 36].