The pathological hallmarks of Alzheimer's disease (AD)—widespread synaptic and neuronal loss and the pathological accumulation of amyloid-beta peptide (Aβ) in senile plaques, as well as hyperphosphorylated tau in neurofibrillary tangles—have been known for many decades, but the links between AD pathology and dementia and effective therapeutic strategies remain elusive. The gene discussed is APP; the disease is early-onset autosomal dominant Alzheimer disease.