Autophagy in Health and Disease - Chapter 20: Autophagic processes in early- and late-onset Alzheimer’s disease

Autophagy plays a fundamental role in maintaining intracellular homeostasis and cell survival by degrading damaged and unnecessary subcellular components via the lysosome. Impaired autophagy is evident in otherwise “normal” elderly individuals and patients with neurodegenerative diseases, such as Alzheimer’s disease (AD). As the most common type of dementia, AD is an age-associated disease with memory loss as the primary clinical feature as well as extracellular Aβ plaques and intracellular Tau tangles as disease-defining pathological features. Recent studies in animal models of AD, AD patient-derived stem cells, and AD postmortem brain tissues suggest that compromised mitophagy/autophagy plays a causative role in AD progression. Supporting this hypothesis, pharmacological approaches to induce mitophagy/autophagy-e.g., the use of the small natural molecule oxidized nicotinamide adenine dinucleotide (NAD+)-slow AD progression in animal models. This chapter reviews the extant literature on autophagy in AD and covers recent progress on the molecular mechanisms of NAD+-dependent mitophagy/autophagy regulation and mechanisms underlying the anti-AD potential of NAD+. Further studies to define the NAD+-mitophagy/autophagy axis may shed light on novel therapeutics to treat AD and potentially provide insights into other neurodegenerative diseases.