Toward the treatment and prevention of Alzheimer's disease: rational strategies and recent progress.

Annu Rev Med 2013 ;64:367-83

Mount Sinai School of Medicine and James J. Peters Veterans Affairs Medical Center, New York, New York 10029, USA.

Alzheimer's disease (AD) is the major cause of late-life brain failure. In the past 25 years, autosomal dominant forms of AD were found to be primariy attributable to mutations in one of two presenilins, polytopic proteins that contain the catalytic site of the γ-secretase protease that releases the amyloid beta (Aβ) peptide. Some familial AD is also due to mutations in the amyloid precursor protein (APP), but recently a mutation in APP was discovered that reduces Aβ generation and is protective against AD, further implicating amyloid metabolism. Prion-like seeding of amyloid fibrils and neurofibrillary tangles has been invoked to explain the stereotypical spread of AD within the brain. Treatment trials with anti-Aβ antibodies have shown target engagement, if not significant treatment effects. Attention is increasingly focused on presymptomatic intervention, because Aβ mismetabolism begins up to 25 years before symptoms begin. AD trials deriving from new biological information involve extraordinary international collaboration and may hold the best hope for success in the fight against AD.

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Source
http://dx.doi.org/10.1146/annurev-med-092611-084441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625402PMC
July 2013
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