Anti-amyloid activity of neprilysin in plaque-bearing mouse models of Alzheimer’s disease

Abstract 

Abnormally high concentrations of β-amyloid peptide (Aβ) and amyloid plaque formation in Alzheimer’s disease (AD) may be caused either by increased generation or by decreased degradation of Aβ. Therefore, activation of mechanisms that lower brain Aβ levels is considered valuable for AD therapy. Neuronal upregulation of neprilysin (NEP) in young transgenic mice expressing the AD-causing amyloid precursor protein mutations (SwAPP) led to reduction of brain Aβ levels and delayed Aβ plaque deposition. In contrast, a comparable increase of brain NEP levels in aged SwAPP mice with pre-existing plaque pathology did not result in a significant reduction of plaque pathology. Therefore, we suggest that the potential of NEP for AD therapy is age-dependent and most effective early in the course of AD pathophysiology.

Keywords:  Transgenic mouse, Alzheimer’s disease, β-Amyloid peptide, Protein stability, Therapy, Neprilysin

Abbreviations:  Aβ, β-amyloid peptide, AD, Alzheimer’s disease, APP, amyloid precursor protein, NEP, neprilysin, Iba-1, ionized calcium binding adapter molecule 1, GFAP, glial fibrillary acidic protein