Effects of intrahippocampal CT105, a carboxyl terminal fragment of β‐amyloid precursor protein, alone/with inflammatory cytokines on working memory in rats

In this study, we examined the effects of a 105 amino acid carboxyl terminal fragment of β-amyloid precursor protein (CT105) and inflammatory cytokines on working memory in rats, by using a three-panel runway set-up. CT105 at 10 nmol/side significantly impaired working memory when it was administered bilaterally into the hippocampus. Furthermore, to elucidate the interaction of CT105 with inflammatory cytokines, we co-administered tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) in combination with CT105. Concurrent injections of CT105 (1.0 nmol/side) and TNF-α (100 ng/side) produced a synergistic deficit of working memory, whereas IL-1β (100 ng/side) combined with CT105 (1.0 nmol/side) did not affect the working memory performance. These results indicate that the CT105-induced impairment of working memory is strongly aggravated by an increase in the level of the inflammatory cytokine TNF-α, which may occur in the brains of patients with Alzheimer's disease.