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Titolo:
CHARACTERIZATION OF NEW POLYCLONAL ANTIBODIES SPECIFIC FOR 40 AND 42 AMINO-ACID LONG AMYLOID-BETA PEPTIDES - THEIR USE TO EXAMINE THE CELL BIOLOGY OF PRESENILINS AND THE IMMUNOHISTOCHEMISTRY OF SPORADIC ALZHEIMERS-DISEASE AND CEREBRAL AMYLOID ANGIOPATHY CASES
Autore:
BARELLI HL; LEBEAU A; VIZZAVONA J; DELAERE P; CHEVALLIER N; DROUOT C; MARAMBAUD P; ANCOLIO K; BUXBAUM JD; KHORKOVA O; HEROUX J; SAHASRABUDHE S; MARTINEZ J; WARTER JM; MOHR M; CHECLER F;
Indirizzi:
CNRS,INST PHARMACOL MOL & CELLULAIRE,UPR 411,660 ROUTE LUCIOLES F-06560 VALBONNE FRANCE CNRS,INST PHARMACOL MOL & CELLULAIRE,UPR 411 F-06560 VALBONNE FRANCE CNRS,URA 1845 MONTPELLIER FRANCE RHONE POULENC RORER VITRY SUR SEINE FRANCE ROCKEFELLER UNIV NEW YORK NY 10021 HOECHST MARION ROUSSEL SOMERVILLE NJ 00000 HOP UNIV,SERV MALAD SYST NERVEUX & MUSCLE STRASBOURG FRANCE INST PATHOL STRASBOURG FRANCE
Titolo Testata:
Molecular medicine
fascicolo: 10, volume: 3, anno: 1997,
pagine: 695 - 707
SICI:
1076-1551(1997)3:10<695:CONPAS>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
PRECURSOR PROTEIN; A-BETA; MISSENSE MUTATIONS; SENILE PLAQUES; CORE PROTEIN; A-BETA-42(43); DEPOSITION; GENE; PHOSPHORYLATION; SECRETION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
H.L. Barelli et al., "CHARACTERIZATION OF NEW POLYCLONAL ANTIBODIES SPECIFIC FOR 40 AND 42 AMINO-ACID LONG AMYLOID-BETA PEPTIDES - THEIR USE TO EXAMINE THE CELL BIOLOGY OF PRESENILINS AND THE IMMUNOHISTOCHEMISTRY OF SPORADIC ALZHEIMERS-DISEASE AND CEREBRAL AMYLOID ANGIOPATHY CASES", Molecular medicine, 3(10), 1997, pp. 695-707

Abstract

Background: In Alzheimer's disease (AD), the main histological lesionis a proteinaceous deposit, the senile plaque, which is mainly composed of a peptide called A beta. The aggregation process is thought to occur through enhanced concentration of A beta 40 or increased production of the more readily aggregating 42 amino acid-long A beta 42 species. Materials and Methods: Specificity of the antibodies was assessed by dot blot, Western blot, ELISA, and immunoprecipitation procedures onsynthetic and endogenous A beta produced by secreted HK293 cells. A beta and p3 production by wild-type and mutated presenilin l-expressingcells transiently transfected with beta APP751 was monitored after metabolic labeling and immunoprecipitation procedures. Immunohistochemical analysis was performed on brains of sporadic and typical cerebrovascular amyloid angiopathy (CAA) cases. Results: Dot and Western blot analyses indicate that IgG-purified fractions of antisera recognize native and denaturated A beta s. FCA3340 and FCA3542 display full specificity for A beta 40 and A beta 42, respectively. Antibodies immunoprecipitate their respective synthetic A beta species but also A beta s and their related p3 counterparts endogenously secreted by transfected human kidney 293 cells. This allowed us to show that mutations on presenilin 1 triggered similar increased ratios of A beta 42 and its p342 counterpart over total A beta and p3. ELISA assays allow detection of about 25-50 pg/ml of A beta s and remain linear up to 750 to 1500 pg/ml without any cross-reactivity. FCA18 and FCA3542 label diffuse and mature plaques of a sporadic AD case whereas FCA3340 only reveals the mature lesions and particularly labels their central dense core. Ln a CAA case, FCA18 and FCA3340 reveal leptomeningeal and cortical arterioles whereas FCA3542 only faintly labels such structures. Conclusions: Polyclonal antibodies exclusively recognizing A beta 40 (FCA3340) or A beta42 (FCA3542) were obtained. These demonstrated that FAD-linked presenilins similarly affect both p342 and A beta 42, suggesting that these mutations misroute the beta APP to a compartment where gamma-secretase, but not alpha-secretase, cleavages are modified. Overall, these antibodies should prove useful for fundamental and diagnostic approaches, as suggested by their usefulness for biochemical, cell biological, andimmunohistochemical techniques.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 11:20:05