Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuronal degeneration and progressive cognitive impairment [55]. While the pathogenesis of AD is not fully understood, AD patients exhibit an accumulation of amyloid plaques formed by oligomerization of the amyloidogenic peptides, Aβ 1–42 and Aβ 1–40, and neurofibrillary tangles formed by tau protein. These plaques and tangles are thought to contribute to neurodegeneration [56]. Inflammatory cytokines may lead to an increase in Aβ peptides, thereby contributing to the progression of AD. The neurotransmitter noradrenaline (NA) can protect neurons from various inflammatory stimuli, including exposure to Aβ peptides. This is thought to occur, in part, by activation of PPARδ. In particular, in primary cultures of rat cortical neurons, Aβ peptides induced cell death as measured by LDH release. The ability of NA to prevent Aβ peptide-induced cell death was decreased in the presence of GW9662, a PPAR antagonist. Moreover, GW0742 blocked cell death to the same degree as NA, as measured by LDH release and Fluoro-Jade B staining [21].
