Neuroinflammation is a critical driving force underlying mild cognitive impairment (MCI) and Alzheimer's disease (AD) pathologies. Activated platelets play an important role in neuroinflammation and have been implicated in AD pathogenic mechanisms. Mean platelet volume (MPV), a marker of platelet activation, is involved in the pathophysiology of a variety of pro-inflammatory diseases. However, little research has been conducted to investigate the relationship between platelet indices and MCI and AD pathogenesis. In this cross-sectional study, we investigated the levels of platelet count, MPV and platelet distribution width (PDW) in 120 AD patients, 120 MCI patients, and 120 non-demented controls. Our study showed that MPV and PDW were significantly lower in patients with AD as compared with either MCI or controls. Moreover, MCI patients had lower MPV and PDW values compared with the controls (P < 0.001). In addition, there is a positive correlation between mini-mental state examination (MMSE) and MPV and PDW, after adjusting age, gender, and body mass index (r = 0.576, P < 0.001 for MPV; r = 0.465, P < 0.001 for PDW, respectively). Multivariate analysis showed that MPV and PDW were significantly associated with MMSE (β = 0.462; P < 0.001 for MPV; β = 0.245; P < 0.001 for PDW; respectively). In conclusion, MPV and PDW were decreased in MCI and AD patients. Further prospective research is warranted to determine the potential clinical application of MPV and PDW as biomarkers in the early diagnosis of AD.
Alzheimer's disease (AD), the most common form of irreversible dementia, is placing considerable burden on the patients, their families, and the society. So far, there is no curative treatment for AD. Mild cognitive impairment (MCI) is considered an early stage of AD.
A growing body of evidence has suggested that neuroinflammation plays a critical role in the development of AD (Agostinho et al., 2010). Moreover, treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk of developing AD (McGeer et al., 1996). Platelets play an important role in neuroinflammation (Horstman et al., 2010). In addition, activated platelets could result in an excessive amyloid-β (Aβ) production (Li et al., 1998). Amyloid precursor protein (APP) has similar concentrations in platelets and brain (Bush et al., 1990). Platelets release more than 90% of circulating APP and contain all the enzymatic machinery to its processing (Li et al., 1994). Therefore, platelet is an ideal model to study AD pathogenetic mechanisms. Some reports showed that platelet APP has been identified as a new diagnostic marker for AD patients (Borroni et al., 2010; Mukaetova-Ladinska et al., 2012). Furthermore, platelet beta-secretase activity and platelet GSK-3β activity are also found to be enhanced in AD patients and correlated with markers of the intracerebral pathology (Forlenza et al., 2005; Johnston et al., 2008; Forlenza et al., 2011). Mean platelet volume (MPV), the most commonly used measure of platelet size, is an indicator of activated platelets and is available in clinical practice. Furthermore, MPV levels are associated with different disease conditions. MPV levels were elevated in diabetes, cardiovascular disease, peripheral artery disease and cerebrovascular disease (Papanas et al., 2004; Muscari et al., 2009; Berger et al., 2010; Chu et al., 2010) and decreased in rheumatoid arthritis and ulcerative colitis (Yuksel et al., 2009; Yazici et al., 2010). Platelet distribution width (PDW), another platelet indice, indicates variation in platelet size and may be useful to distinguish hypoproductive thrombocytopenia (aplastic anemia) and hyperproductive thrombocytopenia (idiopathic thrombocytopenic purpura) (Kaito et al., 2005). However, PDW has not been studied completely.
Recent studies have demonstrated that activated platelets play a pro-inflammatory role in the proteolytic processing of APP into Aβ by ADAMS17 and in the deposition of these proteins (Skovronsky et al., 2001; Evin et al., 2003). Moreover, some studies have showed the important role of MPV as a marker of inflammation, disease activity and efficacy of anti-inflammatory treatment in several chronic inflammatory disorders (Gasparyan et al., 2011). However, aspirin use in AD might pose an increased risk of intracerebral hemorrhage (Bentham et al., 2008; Thoonsen et al., 2010). Therefore, clarifying the exact role of activated platelet in AD is of great clinical importance.
The aim of this study is to evaluate the differences of MPV and PDW in MCI and AD patients.
RT.W participated in study design, data analysis and manuscript preparation. DJ participated in data collection and data analysis. YL participated in data collection and data analysis. QC.L participated in study design, data analysis, manuscript preparation and editing. All authors read and approved the final manuscript.
