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

By Thorlákur Jónsson, J. Atwal, S. Steinberg, J. Snaedal, P. Jonsson, Sigurbjorn Bjornsson, Hreinn Stefansson, P. Sulem, Daniel Fannar Gudbjartsson, Janice A. Maloney and 17 more. Nature, 2012

1,716 citations recorded by the source corpus.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/2b64dde20c5cbbe7e67fdc36b444517255bd495e

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Citations in the corpus

Alzheimer's disease (2018, background): “Conversely, an APP missense mutation (A673T) results in a lifelong decrease in APP cleavage by b-secretase conferring a reduced clinical risk of AD [24].”
The amyloid hypothesis of Alzheimer's disease at 25 years (2016, background): “Even more remarkable has been the identification of an APP missense mutation (A673T) at the second amino acid of the Ab region that results in a lifelong decrease in APP cleavage by b-secretase (Jonsson et al, 2012).”
Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population (2014, background): “5–5%) variants in complex diseases and traits such as triglycerides [1], insulin processing [2], bone mineral density [3], Alzheimer’s disease [4], impulsivity [5], and prostate cancer [6], some of which confer protection from disease [4].”
Rare-variant association analysis: study designs and statistical tests. (2014, methodology): “Similarly, a rare variant associated with Alzheimer disease (MIM 104300) in APP (MIM 104760) 16 and a rare frameshift variant associated with T2D in PDX1 (MIM 600733) 112 were identiﬁed through large-scale imputation with the use of WGS data of Icelanders as a reference.”
Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects (2020, background): “These transgenic cells can be used to elucidate aspects of the molecular mechanisms of AD pathogenesis, particularly those involved in the mutant amyloidogenic pathway affecting the APP coding sequence.(127) The A673V variant near the APP β-secretase cleavage site contributes to AD pathology by incr”
Endoplasmic Reticulum Stress and Associated ROS (2016, background): “In the pathophysiology of AD, oxidative stress is involved in aging and its associated diseases; according to autopsy studies, the PERK-eIf2α pathway is hyper-activated, producing ER stress [96,97].”