Ageing, neurodegeneration and Alzheimer’s disease: the underlying role of oxidative distress

Ageing is associated with an increased susceptibility of developing neurodegenerative diseases, the most prevalent of which is Alzheimer’s disease (AD) (Hou et al., 2019). The brain is particularly susceptible to oxidative distress due to a relatively high oxygen consumption to meet energy demands (around 20% of total intake), a high polyunsaturated fat content and modest antioxidant defences (Cobley et al., 2018). Whilst redox signalling is critical for physiological brain processes (Cobley et al., 2018), this highly dynamic state appears to be imbalanced in AD (Markesbery, 1997). Evidence of oxidative distress in AD is supported by elevated redox active transition metals, lipid, protein and DNA oxidation and a reduction in energy metabolism (Markesbery, 1997). Further, the hallmark pathological features of Amyloid-β accumulation and Tau hyperphosphorylation characterised the AD brain and are both able associated with altered redox balance (Liu et al., 2015). Current options for the treatment of AD are limited to symptom management and only confer modest benefits. The major consensus being that early intervention is critical prior to the establishment of symptom onset. Lifestyle interventions focused on targeting improved dietary intake and increased physical activity may be a much-needed solution to preventing the onset of AD bringing a host of beneficial improvements in cardiometabolic health and physical function (Daskalopoulou et al., 2017, Morris et al., 2017, Samadi et al., 2019). Long term adherence to both an improved diet and increased physical activity are potentially potent non-pharmacological interventions modulating susceptibility to oxidative distress. Developing an understanding of how to optimise dietary manipulation and exercise modality’s will be critical for our future ability to delay the onset of, or even prevent, AD.