Alzheimer’s disease (AD) is characterized by progressive pathological changes in the brain, including accumulation of protein aggregates such as amyloid plaques and neurofibrillary tangles (NFTs). Deposition of these proteins leads to widespread neuronal loss and subsequent cognitive decline. AD-associated pathology also develops in individuals with Down syndrome (DS) and is generally found to precede onset of dementia symptoms. In this chapter, we discuss progressive development of AD pathology, including plaques, NFTs, synaptic dysfunction, neuronal loss, and brain atrophy. Furthermore, we examine similarities and differences in these pathologies between AD and AD/DS. Finally, we review several genetic factors that may contribute to the development of AD.