Abstract
Previous studies have shown sirtuins 3 has neuroprotective effects in regulating oxidative stress and energy metabolism in Alzheimer's disease. However, it is unclear whether other sirtuins are associated with cognitive performance and pathological changes in AD. We used postmortem brains of AD (n= 16), mild cognitive impairment (n= 11) and age- and education-matched cognitively normal (CN, n= 11) subjects from the Banner Sun Health Research Institute Brain Bank. We measured the protein levels of Sirt1-7, synaptic proteins, nucleus signal molecules, AD pathology and cognitive performance. Besides Sirt3 as we previously reported, only Sirt6 level was reduced in the middle temporal gyrus of AD subjects compared to that of CN. This reduction was associated with the severity of tau pathology and poorer cognitive performance, which was consistent with impaired synaptic integrity. This study has shown that Sirt6 is downregulated in AD and is related to synaptic loss. Sirt6 may play a critical role in pathogenesis of AD.
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