Two novel presenilin-1 mutations (Y256S and Q222H) are associated with early-onset Alzheimer's disease

Détails

ID Serval
serval:BIB_567DF68F924F
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Institution
Titre
Two novel presenilin-1 mutations (Y256S and Q222H) are associated with early-onset Alzheimer's disease
Périodique
Neurobiology of Aging
Auteur(s)
Miklossy  J., Taddei  K., Suva  D., Verdile  G., Fonte  J., Fisher  C., Gnjec  A., Ghika  J., Suard  F., Mehta  P. D., McLean  C. A., Masters  C. L., Brooks  W. S., Martins  R. N.
ISSN
0197-4580 (Print)
Statut éditorial
Publié
Date de publication
09/2003
Volume
24
Numéro
5
Pages
655-62
Notes
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S. --- Old month value: Sep
Résumé
Mutations in the gene encoding presenilin 1 (PS-1) account for 50% of early-onset familial Alzheimer's disease (EOFAD) cases. In this study, we identified two missense mutations in the coding sequence of the presenilin (PS-1) gene in two EOFAD pedigrees. AD was confirmed in one pedigree by autopsy. Mutation analysis of PCR products amplified from genomic DNA templates showed two novel PS-1 mutations resulting in Gln222His and Tyr256Ser. The two novel mutations are located within predicted transmembrane domains five (TM-5) and six (TM-6), respectively, and are associated with very early ages of onset. The Tyr256Ser is associated with one of the youngest age of AD onset, 25 years, which is consistent with a drastic change in function of the altered PS-1 protein. A morphometric analysis of the cortical degenerative changes of the Tyr256Ser case, showed severe involvement of the primary motor cortex, which correlated well with the pyramidal changes, including tetraspasticity. Immunoblot analysis showed the Tyr256Ser case had the greatest expression of Abeta(1-40) and Abeta(1-42), which was confirmed by ELISA, compared to other PS-1 mutant FAD cases and age-matched controls and, thus, contributes to the severity of the disease pathology.
Mots-clé
Adult Alzheimer Disease/*genetics Amino Acid Substitution Amyloid beta-Protein/metabolism Blotting, Western Brain/metabolism/pathology DNA Mutational Analysis Enzyme-Linked Immunosorbent Assay Family Health Female Glutamine/genetics Histidine/genetics Humans Immunohistochemistry Membrane Proteins/*genetics *Mutation, Missense Pedigree Peptide Fragments/metabolism Presenilin-1 Senile Plaques/pathology Serine/genetics Tyrosine/genetics
Pubmed
Web of science
Création de la notice
25/01/2008 12:46
Dernière modification de la notice
20/08/2019 15:10
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