Memory impairment and cholinergic dysfunction by centrally administered Abeta and carboxyl-terminal fragment of Alzheimer's APP in mice.

Abstract

SPECIFIC AIMSTo elucidate the in vivo neurotoxicities of carboxyl-terminal fragments of amyloid precursor protein (CTs) and amyloid β peptide (Aβ), we examined cognitive changes using a Y maze and a water maze task after a single intracerebroventricular (i.c.v.) injection of the carboxyl-terminal fragment of amyloid precursor protein (APP) with 105 amino acid (CT105) (68.5, 342 and 685 pmol) or Aβ1–42 (685 pmol) to mice. The changes in acetylcholine (ACh) levels and mitochondrial pyruvate dehydrogenase (PDH) activities were quantified.PRINCIPAL FINDINGS1. A spontaneous alteration behavior was significantly impaired by CT105 and mildly by Aβ1–42Spatial working memory was assessed on day 14 after a single i.c.v. injection of CT105 or Aβ1–42 by recording spontaneous alteration behavior in a Y maze. An i.c.v. injection of CT105 (342 and 685 pmol) induced a more significant decrease in spontaneous alteration behavior than Aβ1–42. None of the peptide treatments affected locomotion, since no difference was obser...