The effect of age and obesity on platelet amyloid precursor protein processing and plasma markers of oxidative stress and inflammation

年龄和肥胖对血小板淀粉样蛋白前体加工以及氧化应激和炎症血浆标志物的影响

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作者:Richard J Elsworthy, Sarah Aldred

Conclusions

The findings presented in this study provide evidence that blood-based biomarkers related to the pathology of AD are altered with age and obesity in otherwise healthy adults. Ageing was more strongly associated with elevated markers of oxidative stress whereas obesity was associated with elevated inflammatory IL-6.

Methods

Ninety participants were recruited to this study to provide one blood sample. Platelet-rich plasma and platelet lysates were collected and the expression of AβPPr, proADAM10 and mADAM10 was assessed by Western blotting. In addition, markers of inflammation (IL-6) and oxidative stress (8-Isoprostane) were assessed in plasma.

Results

Participants were placed into one of four groups based on their age and body mass index (Young/Lean, Young/obese, Old/Lean and Old/Obese). IL-6 was able to significantly distinguish obese from lean participants (AUC of 0.80, SE = 0.05, P < 0.001). Plasma isoprostanes were able to distinguish between both young/old (AUC of 0.73, SE = 0.05, P < 0.01), and obese/non-obese participants (AUC of 0.66, SE = 0.01, P < 0.01). Plasma protein carbonyls could distinguish young and old participants (AUC of 0.69, SE = 0.07 P < 0.02). Old Lean participants had significantly lower mADAM10 expression than both Young Lean and Young Obese participants (p < 0.05). Old obese participants had significantly lower proADAM10 expression compared to both Young Lean and Young Obese (p < 0.05). Both mADAM10 and proADAM10 were significantly decreased with advancing age (p < 0.05). Conclusions: The findings presented in this study provide evidence that blood-based biomarkers related to the pathology of AD are altered with age and obesity in otherwise healthy adults. Ageing was more strongly associated with elevated markers of oxidative stress whereas obesity was associated with elevated inflammatory IL-6.

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