BDI Seminar - Tackling Alzheimer's disease via '3A's: Ageing, Autophagy and Artificial Intelligence

Increased lifespan enables people living longer, but not necessarily healthier. Ageing is arguably the highest risk factor for numerous human diseases, including Alzheimer’s disease (AD); thus understanding the molecular mechanisms of human aging holds the promise of developing interventional and therapeutic strategies for many diseases simultaneously, promoting healthy longevity. Accumulation of damaged mitochondria is a hallmark of aging and age-related AD. However, the molecular mechanisms of impaired mitochondrial homeostasis and their relationship to AD are still elusive. Mitochondrial autophagy (mitophagy) is the cellular self-clearing process of damaged and superfluous mitochondria, and therefore plays a fundamental role in maintaining neuronal function and survival. We hypothesize that age-susceptible defective mitophagy causes accumulation of damaged mitochondria, which in combination with the two AD-defining pathologies, Aβ plaques and tau tangles, further exacerbates AD occurrence and progression. Restoration of mitophagy, through pharmaceutical (e.g., NAD+, passion fruit components, and urolithin A) and genetic approaches, forestalls pathology and cognitive decline in mouse models of AD and improves neuronal function in the AD iPSC-derived neurons. Additionally, we are using artificial intelligence (AI) to propel drug screening and drug design targeting AD and ageing pathways. We are now involved in more than 5 clinical trials on the use of NAD+ precursors to treat AD, and premature ageing diseases, among others.