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PINK1 accumulates on the OMM in response to mitochondrial damage, recruiting Parkin to ubiquitinate mitochondrial proteins and promote autophagosome-mediated clearance [162]

Phosphorylated NQOI then inhibits TBK1 self-association and activates a negative feedback loop that controls TBK1 activation

Increased A and neurofibrillary tangle deposition in the brain subsequently promote further cerebrovascular dysfunction via increased ROS production and inflammation ( Systemic vascular structure and function Though it remains unclear whether reductions in CBF or cerebral metabolism occurs first in the ADRD cascade, mechanical factors such as systemic and cerebral arterial stiffening are additional early stage vascular markers implicated in cerebral hypoperfusion in older adulthood beyond the typical effects of aging (Mitchell, 2011