Karolinska Institutet

About: Karolinska Institutet is a education organization based out in Stockholm, Sweden. It is known for research contribution in the topics: Population & Poison control. The organization has 46212 authors who have published 121142 publications receiving 6008130 citations.

A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline

Abstract: The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-β precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease β-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the β-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms.

Global Public Health Burden of Heart Failure.

Abstract: Heart failure (HF) is a global pandemic affecting at least 26 million people worldwide and is increasing in prevalence. HF health expenditures are considerable and will increase dramatically with an ageing population. Despite the significant advances in therapies and prevention, mortality and morbidity are still high and quality of life poor. The prevalence, incidence, mortality and morbidity rates reported show geographic variations, depending on the different aetiologies and clinical characteristics observed among patients with HF. In this review we focus on the global epidemiology of HF, providing data about prevalence, incidence, mortality and morbidity worldwide.