CH322 - Alzheimer’s Disease: Introduction, Protein Misfolding, Amyloid-β and Tau

Alzheimer’s disease is the most common cause of dementia and represents a growing global health challenge as populations age. In this lecture, we introduce the molecular foundations of Alzheimer’s disease and examine how protein misfolding and aggregation drive neurodegeneration. We begin with an overview of dementia and the increasing prevalence of cognitive disorders in aging populations. The lecture then explores the two major proteins central to Alzheimer’s pathology: amyloid-β (Aβ) and tau. Key topics covered include: • Alzheimer’s disease as a protein misfolding disorder • The amyloid precursor protein (APP) processing pathways • Differences between the amyloidogenic and non-amyloidogenic pathways • Why Aβ42 aggregates more readily than Aβ40 • Formation of amyloid plaques and soluble toxic oligomers • Normal function of tau as a microtubule-associated protein • Hyperphosphorylation of tau and formation of neurofibrillary tangles • The role of protein aggregation in neurodegeneration This lecture provides the biochemical foundation needed to understand later discussions on cellular trafficking failure, lipid metabolism, neuroinflammation, and emerging Alzheimer’s therapies. This content is designed for students studying medicinal chemistry, biochemistry, neuroscience, pharmacology, or neurodegenerative disease biology.