Which disease the London mutation involved in?
['In the present study, we used a new training paradigm in the intelliCage automatic behavioral assessment system to investigate cognitive functions of the transgenic mice harboring London mutation of the human amyloid precursor protein (APP.V717I). ', "The novel approach to study the transgenic mice cognitive abilities presented in this paper offers new insight into cognitive dysfunctions of the Alzheimer's disease mouse model.", "One major hallmark of Alzheimer's disease (AD) is the massive loss of synapses that occurs at an early clinical stage of the disease. In this study, we characterize alterations in spine density and the expression of synapse-associated immediate early gene Arc (activity-regulated cytoskeleton-associated protein) in the hippocampal CA1 regions of two different amyloid precursor protein (APP) transgenic mouse lines before plaque development and their connection to performance in hippocampus-dependent memory tests. The density of mushroom-type spines was reduced by 34% in the basal dendrites proximal to the soma of CA1 pyramidal neurons in 5.5-month-old Tg2576 mice, carrying the Swedish mutation, compared with wild-type littermates. A similar reduction of 42% was confirmed in the same region of 8-month-old APP/Lo mice, carrying the London mutation.", "The London APP mutation (Val717Ile) associated with early shifting abilities and behavioral changes in two Italian families with early-onset Alzheimer's disease.", 'We describe 2 Italian families showing the missense mutation in exon 17 of the amyloid precursor protein gene on chromosome 21 (Val717Ile), known as London mutation.', 'In 1 family, this mutation was responsible for AD in 3 out of 7 siblings and it is also present in a fourth sibling who has only shown signs of executive dysfunction so far. Two subjects of the other family with AD diagnosis were carriers of the same mutation.', 'A pathological hallmark in the brain of an AD patient is extracellular amyloid plaques formed by accumulated beta-amyloid protein (Abeta), a metabolic product of amyloid precursor protein (APP). Studies have revealed a strong genetic linkage in the early-onset familial form (<60 years old) of AD. For example, some mutant APPs are transmitted dominantly and are segregated with inheritance of early onset AD. These mutants facilitate Abeta production. The "Swedish" mutations (APP(SW)) and the "London" mutation (APP(LON)) are examples of these mutants. ', 'The sequences that are effective to silence APP(SW) and APP(LON) as identified in this study may be useful in both in vivo and in vitro studies to investigate the pathophysiological role of APP(SW) and APP(LON) in AD development.', "Here, we show ASP-RNAi against the Swedish- and London-type amyloid precursor protein (APP) variants related to familial Alzheimer's disease using two reporter alleles encoding the Photinus and Renilla luciferase genes and carrying mutant and wild-type allelic sequences in their 3'-untranslated regions. ", "Transgenic mice over-expressing a mutated form of the human amyloid precursor protein (APP, 695 isoform) bearing a mutation associated with Alzheimer's disease (V642I, so-called London mutation, hereafter APPLd2) and wild-type controls were studied at age periods (3 and 10 months) prior to the overt development of neuritic amyloid plaques.", 'The "Swedish" mutations (APP(SW)) and the "London" mutation (APP(LON)) are examples of these mutants.', "Allele-specific silencing of Alzheimer's disease genes: the amyloid precursor protein genes with Swedish or London mutations.", 'Mutations in the amyloid precursor protein gene were the first to be recognized as a cause of Alzheimers disease (AD).We describe 2 Italian families showing the missense mutation in exon 17 of the amyloid precursor protein gene on chromosome 21 (Val717Ile), known as London mutation.In 1 family, this mutation was responsible for AD in 3 out of 7 siblings and it is also present in a fourth sibling who has only shown signs of executive dysfunction so far', 'The London APP mutation (Val717Ile) associated with early shifting abilities and behavioral changes in two Italian families with early-onset Alzheimers disease', 'We analyzed the cytotoxic mechanisms of the London-type AbetaPP mutant, V642I-AbetaPP, in primary cortical neurons utilizing an adenovirus-mediated gene transfer system.', 'We demonstrate that the APP-London and PS1 mutations have additive effects on the increased secretion of betaA4(1-42) relative to betaA4(1-40), indicating that both mutations operate independently.', 'Pathogenic mutations in APP at codon 717 (APP "London") lead to an increased proportion of Abeta 1-42 being produced and secreted.', 'The "Swedish" mutations (APP(SW)) and the "London" mutation (APP(LON)) are examples of these mutants.', "Allele-specific silencing of Alzheimer's disease genes: the amyloid precursor protein genes with Swedish or London mutations.", 'We describe 2 Italian families showing the missense mutation in exon 17 of the amyloid precursor protein gene on chromosome 21 (Val717Ile), known as London mutation.', "The London APP mutation (Val717Ile) associated with early shifting abilities and behavioral changes in two Italian families with early-onset Alzheimer's disease.", 'Such cleavage is promoted by the Swedish and London mutations (APPSwe/Lon) inside the APP gene.', 'We also show that the Swedish and London mutations reduce the amount of APP in the lysosome.', 'This rapid transit to the lysosome is blocked by the presence of either the London or Swedish mutations.']
["London mutation that is the missense mutation in exon 17 of the amyloid precursor protein gene on chromosome 21 (Val717Ile) is involved in Alzheimer's Disease."]
["Alzheimer's Disease", 'AD']