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: 3.5). 01/2011; 3(1):1. DOI: 10.1186/alzrt59
Source: PubMed

ABSTRACT 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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Available from: Bart De Strooper, Aug 15, 2015
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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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    Neuroscience Letters 02/2014; 566. DOI:10.1016/j.neulet.2014.02.034 · 2.06 Impact Factor
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    • "The discovery of monogenic forms of Alzheimer's Disease (AD) has allowed improved knowledge of the physiopathology which, in turn, has allowed the design of new therapeutic strategies. After 20 years of basic and clinical research, understanding the early phases of monogenic AD has become pivotal in order to develop and test the efficacy of the newest target-therapeutic approaches [4]. Even though most monogenic forms of AD have been described in familial early onset AD, recent findings suggest a wider spectrum of clinical presentation, including late-onset and sporadic forms. "
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    ABSTRACT: The discovery of monogenic forms of Alzheimer's Disease (AD) associated with mutations within PSEN1, PSEN2, and APP genes is giving a big contribution in the understanding of the underpinning mechanisms of this complex disorder. Compared with sporadic form, the phenotype associated with monogenic cases is somewhat broader including behavioural disturbances, epilepsy, myoclonus, and focal presentations. Structural and functional imaging show typical early changes also in presymptomatic monogenic carriers. Amyloid imaging and CSF tau/A β ratio may be useful in the differential diagnosis with other neurodegenerative dementias, especially, in early onset cases. However, to date any specific biomarkers of different monogenic cases have been identified. Thus, in clinical practice, the early identification is often difficult, but the copresence of different elements could help in recognition. This review will focus on the clinical and instrumental markers useful for the very early identification of AD monogenic cases, pivotal in the development, and evaluation of disease-modifying therapy.
    11/2013; 2013(6543):689591. DOI:10.1155/2013/689591
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    • "According to the model proposed by Qi-Takahara et al. (Sato et al. 2003; Qi-Takahara et al. 2005), the c-secretase cleavage of the b-CTF is also sequential; firstly the e-cleavage generates Ab48 or Ab49 and the intracellular fragment of APP (AICD). Ab48 and Ab49 are then cleaved by consecutive c-secretase cleavages every three or four amino acids in two production lines: Ab49-Ab46-Ab43-Ab40 and Ab48-Ab45-Ab42-Ab38. Autosomal-dominant AD (ADAD) is a genetic disorder that accounts for less than 1% of all AD cases (Bateman et al. 2011). ADAD has been associated with mutations in three different genes: the APP, PSEN1 or PSEN2 genes. "
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