Mis-sense mutation Val&amp;rarr;Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease

Naruse, Satoshi; Igarashi, Shuichi; Aoki, Kimiko; Kaneko, Kiyotoshi; Iihara, Kuniko; Miyatake, Tadashi; Kobayashi, Hisasgi; Ishii, Takashi; Shimizu, Teruo; Kojima, Takeshi; Tsuji, Shoji

doi:10.1016/0140-6736(91)91612-x

Cited by 260 publications

(51 citation statements)

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“…44,45 The first missense mutation confirmed in the APP gene in FAD was found in a British family 46 and confirmed in a Japanese family in 1991. 47 Since then, 20 pathological mutations in APP have been identified. Most of these are near the proteolytic cleavage sites involved in A␤ production.…”

Section: Molecular Genetics Of Admentioning

confidence: 99%

Transgenic models of Alzheimer’s disease: Learning from animals

2005

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Summary:As the scope of the problem of Alzheimer's disease (AD) grows due to an aging population, research into the devastating condition has taken on added urgency. Rare inherited forms of AD provide insight into the molecular pathways leading to degeneration and have made possible the development of transgenic animal models. Several of these models are based on the overexpression of amyloid precursor protein (APP), presenilins, or tau to cause production and accumulation of amyloid-␤ into plaques or hyperphosphorylated tau into neurofibrillary tangles. Producing these characteristic neuropathological lesions in animals causes progressive neurodegeneration and in some cases similar behavioral disruptions to those seen in AD patients. Knockout models of proteins involved in AD have also been generated to explore the native functions of these genes and examine whether pathogenesis is due to loss of function or toxic gain of function in these systems. Although none of the transgenic lines models the human condition exactly, the ability to study similar pathological processes in living animals have provided numerous insights into disease mechanisms and opportunities to test therapeutic agents. This chapter reviews animal models of AD and their contributions to developing therapeutic approaches for AD.

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Section: Molecular Genetics Of Admentioning

confidence: 99%

Transgenic models of Alzheimer’s disease: Learning from animals

2005

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“…The importance of such findings is likely to be that they will help to elucidate mechanisms more clearly (Hardy, 1991). Not all Alzheimer's disease is familial, and only a handful of the known pedigrees in the world are accounted for by the mutation found in this study (Naruse et al 1991). A community based study in Holland found none out of 197 cases to be associated with this mutation van Duijn, 1992).…”

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confidence: 99%

Research and Alzheimer's disease: an epidemiological perspective

Brayne¹

1993

Psychol. Med.

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“…Several early-onset AD families were shown to be linked with mutations of the ~/A4 amyloid protein precursor (APP) gene (Goate et al, 1991;Murrel et al, 1991;Chartier-Harlin et al, 1991;Mullan et al, 1992a). The mutation producing the 71Wal~Ile substitution at codon 717 of the APP gene had also been identified in Japanese early-onset AD families (Naruse et al, 1991;Yoshioka et al, 1991;Yoshizawa et aI., 1993). Large scale mutational analyses and linkage analyses, however, indicated that the APP gene is not a major causative gene of early-onset FAD (Kamino et al, 1992;Tanzi et al, 1992;Yoshizawa et al, 1993;Fujigasaki et at., 1994).…”

Section: Introductionmentioning

confidence: 99%

Linkage and haplotype analysis of familial early-onset Alzheimer disease in Japanese population

et al. 1995

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SummaryLinkage and haplotype analysis of eleven early-onset Alzheimer disease (AD) familieg was performed in relation to D21S210 and microsatellite DNA polymorphisms localized on chromosome 14q24.3. Linkage analysis of eight informative families out of eleven early-onset AD families disclosed the highest LOD score of 3.45 (0=0.00) at D14S77, while the locus of ~/A4 amyloid protein precursor gene was formally excluded within 10 cM from D21S210, given the evidence of recombinations in five families: Transmission disequilibrium study between the patients and controls without dementia indicated significant differences at D14S43 (p=0.0001) and D14S71 (p=0.02). Association study be- 17, 1995; Revised version accepted June 14, 1995. * To whom correspondence should be addressed. tween genotypes linked or related to onset of AD and those of control also revealed a significant difference at D14S43 (p<0.05), suggesting the existence of linkage disequilibrium. Moreover, the haplotypes at D14S43 linked with the onset of AD indicated a significant relationship with the mean age at onset. These results support that the major locus of earlyonset familial AD is located on 14q24.3, and its close linkage to D14S43 and the existence of allelic heterogeneity were suggested. Received April

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Mis-sense mutation Val→Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease

Cited by 260 publications

References 5 publications

Transgenic models of Alzheimer’s disease: Learning from animals

Transgenic models of Alzheimer’s disease: Learning from animals

Research and Alzheimer's disease: an epidemiological perspective

Linkage and haplotype analysis of familial early-onset Alzheimer disease in Japanese population

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