Advanced age is the largest risk factor for developing Alzheimer disease (AD), with the incidence of AD increasing dramatically with age, and nearly all patients with AD manifesting symptoms after age 65 years (late-onset AD [LOAD]).1 However, approximately 5% of those with AD experience onset before age 65 years and are classified as having early-onset AD (EOAD).2 Despite the low prevalence of EOAD compared with LOAD, studying EOAD has led to seminal discoveries in AD. The most famous example is Dr Alois Alzheimer’s examination of the brain of Auguste D., a patient who initially presented with symptoms of dementia at age 51 years, which led to the histopathological findings of extracellular neuritic plaques and intracellular neurofibrillary tangles that remain the neuropathological hallmarks of AD.3 Several decades later, genetic studies in familial EOAD with autosomal dominant transmission resulted in the discovery of the 3 genes currently known to be causative for AD (amyloid precursor protein, presenilin 1, and presenilin 2).2
Ishii M. Apolipoprotein B as a New Link Between Cholesterol and Alzheimer Disease. JAMA Neurol. Published online May 28, 201976(7):751–753. doi:10.1001/jamaneurol.2019.0212
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