Alzheimer’s Disease: Etiology, Neuropathology and Pathogenesis

ABSTRACT Alzheimer’s disease is the most common form of dementia and the most common neurodegenerative disease. It manifests as a decline in short-term memory and cognition that impairs daily behavior. Most cases of Alzheimer’s disease are sporadic, but a small minority of inherited forms allow gene identification which, together with neuropathology, yields important clues about the wider causes. Environmental and metabolic risk factors, including inflammation and vascular impairment, play a role in disease onset and progression. While neuronal atrophy and a loss of synapses occur throughout the cerebral cortex, we lack a full understanding of how this arises. The known hallmarks of Alzheimer’s disease include amyloid-β plaques and neurofibrillary tau tangles and while extensive research has been carried out throughout the past few decades, the exact role of these protein aggregates in the disease remains elusive. In this chapter, we discuss mechanisms that have been implicated, including inflammation, mitochondrial dysfunction, oxidative stress and changes in protein clearance.