Mutation of the Alzheimer's Disease Amyloid Gene in Hereditary Cerebral Hemorrhage, Dutch Type

Levy, Efrat; Carman, M. D.; Fernandez-Madrid, Ivan; Power, Michael D.; Lieberburg, Ivan; Duinen, Sjoerd G. van; Bots, G. Th. A. M.; Luyendijk, W; Frangione, Blas

doi:10.1126/science.2111584

Cited by 1,286 publications

(724 citation statements)

References 30 publications

Supporting

Mentioning

709

Contrasting

Unclassified

Order By: Relevance

“…Mutations have been found in genes encoding various amyloid proteins in familial amyloidoses with an autosomal dominant mode of inheritance, such as hereditary cerebral hemorrhage with amyloidoses, Icelandic type (24) and Dutch type (25), several types of familial amyloid polyneuropathy (PAP) (26), Gerstmann-Sträussler-Scheinker syndrome (27), and FAF, described here. Point mutation may affect the regulatory mechanisms of expression of the mRNAs or the post-translational processing of the precursor protein, thus enhancing amyloid fibril formation and deposition .…”

Section: Resultsmentioning

confidence: 97%

“…Amplification reactions in a volume of 100 pl contained 1 Rg of DNA, 0 .125 AM ofeach primer, and 2 .5 u of Taq polymerase in reaction buffer (PerkinElmer-Cetus, Norwalk, CT) . The samples were subjected to 25 cycles set at 94°C for 1 min to denature the DNA, 56°C for 30 s to anneal the primers, and 72°C for 1 min to extend the annealed primers.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mutation in gelsolin gene in Finnish hereditary amyloidosis.

Levy

Haltia

Fernandez-Madrid

et al. 1990

The Journal of Experimental Medicine

143

View full text Add to dashboard Cite

Familial amyloidosis, Finnish type (FAF), is an autosomal dominant form of familial amyloid polyneuropathy. The novel amyloid fibril protein found in these patients is a degradation fragment of gelsolin, an actin-binding protein. We found a mutation (adenine for guanine) at nucleotide 654 of the gelsolin gene in genomic DNA isolated from five FAF patients. This site is polymorphic since the normal allele was also present in all the patients tested. This mutation was not found in two unaffected family members and 11 normal controls. The A for G transition causes an amino acid substitution (asparagine for aspartic acid) that was found at position 15 of the amyloid protein. The mutation and consequent amino acid substitution may lead to the development of FAF.

show abstract

Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Mutation in gelsolin gene in Finnish hereditary amyloidosis.

Levy

Haltia

Fernandez-Madrid

et al. 1990

The Journal of Experimental Medicine

143

View full text Add to dashboard Cite

show abstract

“…Two patients with this disease were found to have a point mutation resulting in the replacement of glutamic acid by glutamine at position 22 of the fl/A4 amyloid protein [26]. This mutation may make the fl/A4…”

Section: Resultsmentioning

confidence: 99%

Cross‐linking of a synthetic partial‐length (1–28) peptide of the Alzheimer β/A4 amyloid protein by transglutaminase

1993

View full text Add to dashboard Cite

Cerebral deposits of iliA4 amyloid protein is a pathologic sign of Alzheimer's disease. A synthetic partial-length (I 28) peptide of this protein contains one glutamine and two lysine residues. Here we show that this peptide can be a substrate oftransglutaminase, which catalyzes cross-linking between glutamine and lysine residues in peptides, by demonstrating the formation of multimeric peptides due to the action of this enzyme. A modified (Lys 2s to L-norleucine) version of the synthetic peptide was also cross-linked, but another modified version (Lys ~6 to L-norleucine) was very poorly cross-linked, indicating that Lys 16 is involved exclusively in the cross-linking of the partial-length peptide catalyzed by transglutaminase.Transglutaminase; Amyloid beta-protein; Alzheimer's disease.

show abstract

“…HCHWA-D is an autosomal dominant disease caused by a glutamine to glutamic acid substitution at amino acid position [95] . The main symptoms are (recurrent) hemorrhagic stroke and dementia in the 5th or 6th decade of life [96] .…”

Section: Hemorrhagic Strokementioning

confidence: 99%

Genetics of stroke

Guo

Liu

2010

Acta Pharmacol Sin

View full text Add to dashboard Cite

Stroke is the second most common cause of death and the most common cause of disability in developed countries. Stroke is a multifactorial disease caused by a combination of environmental and genetic factors. Numerous epidemiologic studies have documented a significant genetic component in the occurrence of strokes. Genes encoding products involved in lipid metabolism, thrombosis, and inflammation are believed to be potential genetic factors for stroke. Although a large group of candidate genes have been studied, most of the epidemiological results are conflicting. Studies of stroke as a monogenic disease have made huge progress, and animal models serve as an indispensable tool to dissect the complex genetics of stroke. In the present review, we provide insight into the role of in vivo stroke models for the study of stroke genetics.

show abstract

Mutation of the Alzheimer's Disease Amyloid Gene in Hereditary Cerebral Hemorrhage, Dutch Type

Cited by 1,286 publications

References 30 publications

Mutation in gelsolin gene in Finnish hereditary amyloidosis.

Mutation in gelsolin gene in Finnish hereditary amyloidosis.

Cross‐linking of a synthetic partial‐length (1–28) peptide of the Alzheimer β/A4 amyloid protein by transglutaminase

Genetics of stroke

Contact Info

Product

Resources

About