How neurons die in Alzheimer's disease: Implications for neuroinflammation

Abstract

Despite the long-standing observation of vast neuronal loss in Alzheimer's disease (AD) our understanding of how and when neurons are eliminated is incomplete. While previous investigation has focused on apoptosis, several novel forms of cell death (i.e. necroptosis, parthanatos, ferroptosis, cuproptosis) have emerged that require further investigation. This review aims to collect evidence for different modes of neuronal cell death in AD and to also discuss how these different forms of cell death may impact the neuroinflammatory environment that prevails in the AD brain. Improved understanding of how neurons die may help to delineate disease pathogenesis, provide insights toward treatment, and aid in the development of improved animal models of AD.

Keywords: Alzheimer's disease; Amyloid beta; Apoptosis; Cell death; Disease-associated microglia; Ferroptosis; Microglia; Multiple sclerosis; Necroptosis; Necrosis; Neurodegenerative disease; Neuroimmunology; Neuroinflammation; Parthanatos; Phagocytosis; Pyroptosis.