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

Department of Neurology, Washington University School of Medicine, 660 S, Euclid, Campus Box 8111, St Louis, MO 63110, USA. .
Alzheimer's Research and Therapy (Impact Factor: 3.98). 01/2011; 3(1):1. DOI: 10.1186/alzrt59
Source: PubMed


Autosomal-dominant Alzheimer's disease has provided significant understanding of the pathophysiology of Alzheimer's disease. The present review summarizes clinical, pathological, imaging, biochemical, and molecular studies of autosomal-dominant Alzheimer's disease, highlighting the similarities and differences between the dominantly inherited form of Alzheimer's disease and the more common sporadic form of Alzheimer's disease. Current developments in autosomal-dominant Alzheimer's disease are presented, including the international Dominantly Inherited Alzheimer Network and this network's initiative for clinical trials. Clinical trials in autosomal-dominant Alzheimer's disease may test the amyloid hypothesis, determine the timing of treatment, and lead the way to Alzheimer's disease prevention.

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    • "An emerging view is that therapeutic success may only be possible with intervention very early in the disease course. This has motivated the development of treatment trials specifically for FAD, which offers the possibility of treating individuals at a preclinical disease stage (Bateman et al., 2011; Reiman et al., 2010). Furthermore, the young age of patients with FAD, which typically manifests in the 30se50s, means that comorbidities such as atherosclerotic cerebrovascular "
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    ABSTRACT: Familial Alzheimer's disease (FAD) treatment trials raise interest in the variable occurrence of cerebral amyloid angiopathy (CAA); an emerging important factor in amyloid-modifying therapy. Previous pathological studies reported particularly severe CAA with postcodon 200 PSEN1 mutations and amyloid beta coding domain APP mutations. As CAA may manifest as white matter hyperintensities (WMH) on magnetic resonance imaging, particularly posteriorly, we investigated WMH in 52 symptomatic FAD patients for associations with mutation position. WMH were visually rated in 39 PSEN1 (18 precodon 200); 13 APP mutation carriers and 25 healthy controls. Ten PSEN1 mutation carriers (5 precodon 200) had postmortem examination. Increased WMH were observed in the PSEN1 postcodon 200 group and in the single APP patient with an amyloid beta coding domain (p.Ala692Gly, Flemish) mutation. WMH burden on MRI correlated with severity of CAA and cotton wool plaques in several areas. The precodon 200 group had younger ages at onset, decreased axonal density and/or integrity, and a greater T-lymphocytic response in occipital deep white matter. Mutation site contributes to the phenotypic and pathological heterogeneity witnessed in FAD.
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    • "Alzheimer's disease (AD) is the most common cause of dementia (Lohmann et al., 2012). AD causes an insidious and progressive loss of cognitive function and independence, taking a heavy personal and financial toll on patients and affected families (Bateman et al., 2011). A minority of AD patients begins presenting symptoms before the age of 65 years. "
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    • "Decoding AD gene mutations is important because not only does it provide a more sophisticated understanding of the pathobiology in EO-FAD, but might assist in the identification of at-risk patients for early treatment interventions in the future [11] [12]. In this report, we will present the clinical, neuropsychological, imaging and molecular data of two family members with a novel PSEN1 missense mutation. "
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