Autosomal dominant Alzheimer disease (ADAD) accounts for less than 1% of those affected by Alzheimer disease (AD) in the world’s population. However, because temporal progression is fairly predictable and the underlying neuropathology and clinical presentation parallel that of late-onset sporadic AD (sAD), it provides an important human model for research on more prevalent sAD. More than 500 families with more than 200 known mutations in the amyloid precursor protein and presenilin genes associated with amyloid-β (Aβ) production have been identified. Much of what we know about the molecular and neuropathologic origins of AD stems from discoveries in these genetic variants and associated animal models. Genetic Aβ overproduction disorders offer researchers the opportunity to evaluate the natural progression of AD in a highly predictable model. Application of fluid biomarkers and neuroimaging tools in the study of ADAD can aid in the understanding of early neuropathological changes and assist in identifying predictive presymptomatic markers of clinically significant AD. On the other hand, although ADAD has many similarities in clinical progression and pathology to sAD, these are arguably diseases with distinct inciting mechanisms that lead to similar downstream effects.
Fleisher AS. The Value of Biomarker Comparisons Between Autosomal Dominant and Late-Onset Alzheimer Disease. JAMA Neurol. 2014;71(9):1087-1088. doi:10.1001/jamaneurol.2014.1747