TABLE 2.

Experimental approaches for increasing ABCA1 expression.

Experimental approach	References
ABCA1 overexpressiona	Wahrle et al., 2008
Bexaroteneb	Cramer et al., 2012; Balducci et al., 2015; Skerrett et al., 2015; Muñoz-Cabrera et al., 2019
Extra virgin olive oilc	Helal et al., 2013
LXR agonistsd	Fukumoto et al., 2002; Koldamova et al., 2003; Sun et al., 2003; Burns et al., 2006; Donkin et al., 2010; Fitz et al., 2010; Loane et al., 2011; Vanmierlo et al., 2011
PPAR-α and PPAR-γ activatione	Chawla et al., 2001; Chinetti et al., 2001; Xia et al., 2005
Retinoic acid receptor agonistsf	Costet et al., 2003
Verapamilg	Suzuki et al., 2004

^aOverexpression of ABCA1 decreased cerebral Aβ burden and SPs in PDAPP transgenic mice.

^bBexarotene lowered cerebral Aβ in APP/PS1 and C57Bl/6 mice (Cramer et al., 2012) and a later study had similar findings in APP/PS1 mice (Skerrett et al., 2015). Bexarotene treatment lowered astrogliosis and reactive microglia, while increasing NeuN expression, in 3×Tg-AD mice (Muñoz-Cabrera et al., 2019). Conversely, Balducci et al., 2015, found no reduction in SPs in Bexarotene-treated TASTPM mice.

^cHealthy human subjects consumed extra-virgin olive oil for 12 weeks. Plasma-derived HDL from these subjects increased in vitro cholesterol efflux from human monocyte-derived macrophages.

^dTreatment of neuroblastoma cells with a LXR ligand increased their secretion of Aβ40 and Aβ 42 (Fukumoto et al., 2002). Exposure of primary neurons and glia from embryonic rat brain to LXR ligands increased their cholesterol efflux (Koldamova et al., 2003). Incubation of APP-expressing cells with LXR activators lowered their Aβ production independently of cellular lipid efflux (Sun et al., 2003). Treatment of wild-type mice with a LXR agonist increased plasma cholesterol and decreased cerebral Aβ (Burns et al., 2006). Administration of a LXR ligand to APP23 mice lowered cerebral Aβ, including SPs (Fitz et al., 2010), with similar results in APP/PS1 mice (Donkin et al., 2010). Pre- and post-injury treatment of C57Bl/6 mice undergoing traumatic brain injury (TBI) reduced their TBI-related increase in cerebral Aβ (Loane et al., 2011). Administration of a LXR activator to APPSLxPS1mut mice improved their memory functions without influencing cerebral Aβ levels (Vanmierlo et al., 2011).

^ePPAR-γ treatment of tissue plasminogen activator-differentiated THP-1 macrophages increased cholesterol efflux (Chawla et al., 2001), and similar results were found for PPAR-α and PPAR-γ activation of human macrophages (Chinetti et al., 2001). Anthocyanin increased PPAR-γ-mediated cholesterol efflux from mouse peritoneal macrophages (Xia et al., 2005).

^fRetinoic acid receptor activators increased ABCA1 expression and cholesterol efflux in mouse peritoneal macrophages, and ABCA1 expression in human monocytes/macrophages (Costet et al., 2003).

^gThe calcium channel blocker Verapamil increased ABCA1 expression and cholesterol efflux cAMP analog-treated RAW264 (mouse macrophage) cells (Suzuki et al., 2004). ABCA1, ATP binding cassette subfamily A member 1; LXR, liver X receptors; PPAR-α, peroxisome proliferator-activated receptor-α; PPAR-γ, peroxisome proliferator-activated receptor-γ.