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J Geriatr Psychiatry Neurol. 2005 Dec;18(4):228-33.

What the study of persons at risk for familial Alzheimer's disease can tell us about the earliest stages of the disorder: a review.

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  • UCLA Alzheimer Disease Center, Los Angeles, CA 90095-1769, USA. jringman@mednet.ucla.edu


As the proportion of elderly persons continues to expand, understanding the pathobiology of Alzheimer's disease and being able to diagnose it at an early stage become more critical. A minority of Alzheimer's disease cases are inherited as a fully-penetrant, autosomal dominant trait with a young age of onset. The molecular study of the pathogenic mutations has led to insights regarding the etiology of sporadic Alzheimer's disease. Clinical studies in persons at risk for these mutations have confirmed early episodic memory and executive deficits in Alzheimer's disease and suggested that dysphoria may precede the cognitive changes of Alzheimer's disease. Imaging studies have indicated that medial temporal lobe atrophy begins 3 to 4 years before cognitive symptoms, and quantitative cerebral metabolic changes are also present from early on. Studies of biochemical markers suggest that elevations of plasma A 1-42 occur early in familial Alzheimer's disease but that tau may not be elevated in cerebrospinal fluid until the disease is more advanced.

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