differentiates the APP gene from the closely related APLP1 and APLP2 genes that are not linked to AD, is much less clear. Genetic variations in the APP promoter correlate with AD risk (Lahiri et al., 2005; Brouwers et al., 2006), and APP gene duplications cause early-onset AD (Rovelet-Lecrux et al., 2006; Sleegers et al., 2006), showing that APP expression is indeed important for AD pathogenesis. The finding that ApoE increases APP transcription 4–6 fold in human neurons by activation of cFos-containing AP-1 transcription factors suggests that it may be possible to influence APP transcription pharmacologically as an approach to AD prevention or even therapy.
