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Autosomal-dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease

DOI: 10.1186/alzrt59

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Alzheimer's disease (AD) afflicts an estimated 24 million people in the world, with an expected increase to over 80 million people by the year 2040 [1]. AD causes an insidious and progressive loss of cognitive function and independence, taking a heavy personal and financial toll on the patient and the family. Because of the severity and increasing prevalence of the disease in the population, it is urgent that better treatments be developed.The only identified deterministic factors for the development of AD are the presence of mutations in one of three genes - amyloid precursor protein (APP), presenilin 1 (PSEN1) or presenilin 2 (PSEN2) - or duplication of APP. 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 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 urgen


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