Approximately 50% of people from these kindreds are mutation carriers destined to develop dementia of the Alzheimer’s type, generally at an early age (~30 to 50 years). In the present http://www.selleckchem.com/products/Axitinib.html review, we define autosomal-dominant Alzheimer’s disease (ADAD) as dominantly inherited AD with pathological confirmation. Other terms, such as familial AD and early-onset AD, may encompass ADAD, but may also include AD from nondominant causes such as the apolipoprotein E4 allele or sporadic Alzheimer’s disease (SAD). Although ADAD represents fewer than 1% of all AD cases, it is a critically important area of study because the pathological features of the disease are similar to the more common sporadic form, because causative mutations have known biochemical consequences that are believed to underlie the much more prevalent sporadic form of the disease, and because it is possible to identify and study presymptomatic individuals decades before they are destined to develop clinical disease.

The opportunity to determine the sequence of biomarker changes in presymptomatic gene carriers who are destined to develop AD is likely to reveal critical information about the pathobiological cascade that culminates in symptomatic disease. The realization that AD is a major and growing public health problem with aging populations has added urgency to the search for improved therapeutics. Many proposed treatments for AD currently target slowing or halting of the underlying disease (that is, putative disease-modifying interventions), but they are not likely to reverse the extensive neuronal death already present at the onset of symptoms.

For individuals and families at risk for ADAD, such interventions have the potential to delay or even prevent dementia in asymptomatic individuals, in addition to slowing progression in those with symptoms. These at-risk individuals offer a potential proof of concept for presymptomatic disease modification, with implications for AD more generally. ADAD families have provided important insights into the pathogenesis of AD in the past several decades. Discovery of human genetic mutations has facilitated the development of the transgenic animal models used in AD research today. Knowledge of the molecular mechanisms of the identified mutations has catalyzed Carfilzomib identification of the causative pathogenic events in AD in humans.

Indeed, this avenue of research has provided the most compelling case for a unifying theory of AD. In addition to contributing to exactly advances in the basic scientific understanding of AD, ADAD families represent an ideal population for preventative and treatment trials for several reasons. First, there is near certainty (~100%) regarding development of the disease with a known mutation that enables prevention studies and increases the power of treating minimally or presymptomatic patients.