Previously, we reported that nicotine modulates expression of mRNA and protein levels of the APP and APLP2 genes in different mouse brain regions and in SH-SY5Y neuroblastoma cells (Gutala et al. 2006). Furthermore, there are the following evidences supporting the role of APBB1 in ND. First, APBB1 has been shown to influence learning and memory in Fe65 knockout mice (Wang et al. 2004), which is associated with the pharmacological effect of nicotine on the cognitive behavior. Second, it is known that APBB1 is involved in the modulation of β-amyloid secretion (Pietrzik et al. 2002, 2004; Sabo et al. 1999), suggesting that it regulates proteolytic events associated with Alzheimer’s disease (AD) pathogenesis. Third, epidemiological studies suggest that tobacco smoking is inversely correlated with neurodegenerative diseases such as AD and Parkinson’s disease (PD) (Birrenbach and Bocker 2004; Fratiglioni and Wang 2000; Sacco et al. 2004). These facts strongly indicate that APBB1 is a plausible candidate for a genetic study on ND.
