Inflammation and Oxidation: A Link in Alzheimer’s Disease Pathogenesis

Over the past three decades, two paradigms have been developing that largely describe the difference between normal and pathological brain aging: Namely, the twin paradigms of neural oxidative stress and neuroinflammation. These two concepts both emerged amidst an intellectual environment of either casual neglect or antipathy but have come to permeate much basic and applied neuroscience research. Current science has come to understand that these two phenomena are mutually but subtly linked to such an extent as to be practically inseparable. In Alzheimer’s disease (AD) both neural oxidative stress and neuroinflammatory events are crucial components of the neurodegenerative landscape. Both appear to arise, in part, as consequences of the classic features of AD pathology namely amyloid peptide (Aβ)-containing senile plaques and neurofibrillary tangles (NFTs). Viewed from a different perspective, however, oxidative stress and neuroinflammation also contribute fundamentally to cell biological changes that predispose the AD brain to these classic histopathologies. This review will attempt to summarize the current state of knowledge regarding neural oxidative stress in AD, with emphasis on mechanistic connections between the two phenomena, and their joint relationship to both plaques and tangles.