Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene

  title={Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene},
  author={Evgeny I. Rogaev and Robin Sherrington and Ekaterina Rogaeva and Georges Lévesque and Masaki Ikeda and Y. Liang and H. Chi and C. Lin and K. Holman and Takehide Tsuda and Lynn Mar and Sandro Sorbi and Benedetta Nacmias and Silvia Piacentini and Luigi A. Amaducci and Ilya Chumakov and Daniel Cohen and Lars Lannfelt and Paul E. Fraser and Johanna M. Rommens and Peter St. George-Hyslop},
WE report the cloning of a novel gene (E5-1) encoded on chromosome 1 which has substantial nucleotide and amino-acid sequence similarity to the S182 gene on chromosome 14q24.3. Mutations, including three new missense mutations in the S182 gene, are associated with the AD3 subtype of early-onset familial Alzheimer's disease (AD)1. Both the E5-1 and the S182 proteins are predicted to be integral membrane proteins with seven membrane-spanning domains, and a large exposed loop between the sixth and… Expand
A novel missense mutation in the presenilin-1 gene in a familial Alzheimer's disease pedigree with abundant amyloid angiopathy
Results indicate that a mutation at the C-terminus of the third transmembrane domain in the presenilin-1, which is a novel site for mutations, may play a key role in Alzheimer's pathogenesis. Expand
A novel mutation in the predicted TM2 domain of the presenilin 2 gene in a Spanish patient with late-onset Alzheimer's disease
The first mutation in a presenilin gene in a Spanish AD case is reported, which is the third mutation detected for the PS-2 gene. Expand
Chromosome 14 familial Alzheimer’s disease: the clinical and neuropathological characteristics of a family with a leucine→serine (L250S) substitution at codon 250 of the presenilin 1 gene
PS1 L250S familial Alzheimer's disease is an early onset form of Alzheimer’s disease with clinical features similar to other reported familial Alzheimer”s disease pedigrees, except that seizures were absent. Expand
Identification and expression analysis of a potential familial Alzheimer disease gene on chromosome 1 related to AD3.
  • J. Li, J. Ma, H. Potter
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1995
The existence of a gene encoding a seven transmembrane domain protein very similar to that encoded by AD3 in structure and sequence is reported and suggests a possible role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. Expand
Alzheimer's disease associated with mutations in presenilin 2 is rare and variably penetrant.
Analysis of additional members of a pedigree known to segregate a Met239Val mutation in PS-2 revealed that the age of onset of symptoms is highly variable (range 45-88 years), and this variability is not attributable to differences in ApoE genotypes. Expand
Familial Alzheimer's disease genes in Japanese
The data indicate that PS-1 mutations account for 20.0% of early onset FAD cases in Japan, which could be explained only partially by apolipoprotein E epsilon4, important FAD genes or risk-factor genes remain to be identified. Expand
Clinicopathological features of familial Alzheimer's disease associated with the M139V mutation in the presenilin 1 gene. Pedigree but not mutation specific age at onset provides evidence for a further genetic factor.
The pattern of cognitive decline was similar in both families: early memory loss was followed soon after by loss of arithmetic skills while naming and object perception skills were relatively preserved, and the diagnosis of Alzheimer's disease was confirmed with typical histopathology in one individual from each family. Expand
Gene identification in Alzheimer's disease.
Intense efforts are underway to identify additional susceptibility genes and promising regions on chromosomes 6, 9, 10 and 12 have been identified through whole genome scans, and the genetic basis of several other non-AD inherited dementias has been unravelled. Expand
Novel presenilin-1 Y159F sequence variant associated with early-onset Alzheimer's disease
A novel nucleotide sequence variant was discovered in one allele for presenilin-1, corresponding to a missense tyrosine-to-phenylalanine change at codon 159 (Y159F), and likely represents a mutation causing familial, early-onset Alzheimer's disease. Expand
Genetics of Alzheimer's disease.
Genetic variability at the apoliprotein E locus is a major determinant of late onset Alzheimer's disease and the 'amyloid cascade hypothesis', which proposes that overproduction or failure to clear the peptide A beta 42 is always central to the disease. Expand


Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
A minimal cosegregating region containing the AD3 gene is defined, and at least 19 different transcripts encoded within this region corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein. Expand
Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14.
Evidence indicates a familial Alzheimer's disease locus on chromosome 14, which is found in early-onset non-Volga German kindreds, and results for the Volga German families were either negative or nonsignificant for markers in this region. Expand
Familial alzheimer's disease in american descendants of the volga germans: Probable genetic founder effect
Five families are described in which autopsy‐confirmed presenile Alzheimer's disease (AD) has occurred in men and women over multiple generations consistent with autosomal dominant inheritance, and it is likely that the AD in these families represents an autosome dominant gene inherited from one ancestor (the founder effect). Expand
Studies in aging of the brain
Alzheimer disease was transmitted in a pattern consistent with an autosomal dominant trait in three families and one patient had histologically confirmed Alzheimer disease, whereas her sister had proved spongiform encephalopathy, suggesting a link between familial Alzheimer disease and transmissible dementia. Expand
Cloned glutamate receptors.
The application of molecular cloning technology to the study of the glutamate receptor system has led to an explosion of knowledge about the structure, expression, and function of this most importantExpand
A simple method for displaying the hydropathic character of a protein.
A computer program that progressively evaluates the hydrophilicity and hydrophobicity of a protein along its amino acid sequence has been devised and its simplicity and its graphic nature make it a very useful tool for the evaluation of protein structures. Expand
Basic local alignment search tool.
A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP)Expand