INVESTIGADORES
CASTAÑO Eduardo Miguel
artículos
Título:
Differential cerebral deposition of IDE and NEP in sporadic and familial Alzheimer's disease.
Autor/es:
DORFMAN VB; PASQUINI L; RUIDAVETS M; LOPEZ-COSTA JJ; VILLEGAS A; TRONCOSO JC; LOPERA F; CASTAÑO EM; MORELLI L
Revista:
NEUROBIOLOGY OF AGING
Editorial:
ELSEVIER SCIENCE INC
Referencias:
Lugar: Amsterdam; Año: 2010 vol. 31 p. 1743 - 1757
ISSN:
0197-4580
Resumen:
Alzheimer?s disease (AD) is characterized by amyloid β (Aβ) accumulation
in the brain and is classified as familial early-onset (FAD) or
sporadic late-onset (SAD). Evidences suggest that deficits in the brain
expression of insulin degrading enzyme (IDE) and neprilysin (NEP), both
proteases involved in amyloid degradation, may promote Aβ deposition in
SAD. We studied by immunohistochemistry IDE and NEP cortical expression
in SAD and FAD samples carrying the E280A presenilin-1 missense
mutation. We showed that IDE, a soluble peptidase, is linked with
aggregated Aβ40 isoform while NEP, a membrane-bound protease, negatively
correlates with amyloid angiopathy and its expression in the senile
plaques is independent of aggregated amyloid and restricted to SAD
cases. NEP, but not IDE, is over-expressed in dystrophic neurites, both
proteases are immunoreactive in activated astrocytes but not in
microglia and IDE was the only one detected in astrocytes of white
matter from FAD cases. Collectively, our results support the notion that
gross conformational changes involved in the modification from
?natively folded-active? to ?aggregated-inactive? IDE and NEP may be a
relevant pathogenic mechanism in SAD.