Finally, ADAD research participants are highly motivated, relatively young, and have minimal co-morbidities. By engaging those at risk for ADAD, uniquely informative scientific information about disease progression, biomarkers and changes due to therapeutic treatments are expected to lead to advancements in drug development. Disease-modifying selleck chemicals therapeutics have been largely developed with animal models based on human disease-causing mutations. ADAD caused by known mutations most closely resembles those models, and therefore is more likely to respond to disease-modifying treatments. Results from treatment trials in ADAD will bridge cellular and mouse therapeutic research with SAD therapeutic research.

Because the clinical and pathological phenotypes of ADAD are similar to the more common late-onset AD, drugs that prove successful in the prevention or delay of dementia for ADAD are likely to provide guidance for future prevention and disease modification in late-onset AD. Successful implementation of prevention and symptomatic studies will therefore inform about the causes of AD and will provide guidance for future therapeutic development. In the present review, we present historical and current information about ADAD, including: discovery of the genetic mutations; clinical, pathological, imaging and biomarker findings; the explosion of understanding about AD based on basic science studies of genetic mutations and development of AD animal models from the mutations; and an international multicenter effort to understand the cascade of events leading to AD toward future trials to treat – and even prevent – the onset of dementia in those with mutations.

A brief history of autosomal-dominant Alzheimer’s disease research Provocative supportive evidence indicates that Dr Alois Alzheimer’s first case may have been ADAD. This case (August D), described in 1906, was early onset, possibly familial, and from a region of Germany associated with the PSEN2 Volga-German mutation [2]. The first documented cases of familial AD were identified in early-onset dementia with pathological confirmation [3,4]. Other notable early studies identified pedigrees in which more than 10 individuals over five generations were affected by early-onset AD [5]. Affected individuals developed symptoms before age 60 with progressive amnesia and other signs of cortical cognitive impairment as seen in late-onset SAD [6].

Neuropathological examination of these early cases demonstrated extensive amyloid and neurofibrillary pathology with neuronal loss and gliosis. In 1963, a case series with early-onset AD in 11 of 26 children with an affected parent and no affected individuals in the pedigree without an affected parent developing the disease suggested that early-onset Cilengitide http://www.selleckchem.com/products/MDV3100.html AD was the result of a fully penetrant autosomal-dominant mutation [7].