Table 2.

Summary of the curcumin effects on genes

Summary of gene effects	Gene	Role	Low curcumin	High curcumin
Innate immune, neuroprotective-associated microglial phenotype	TREM2	Triggering receptor on myeloid cells, central microglial hub gene, regulating tyrosine kinase signaling in microglia; loss of function increases AD risk (Cherry et al., 2014,Kamphuis et al., 2016; Keren-Shaul et al., 2017)	↑	ns
	TyroBP (DAP12)	Central microglial hub gene coding for adapter protein for TREM2 (and Fc receptor) coupling to tyrosine kinase signaling in microglia, with genetic variants that impact AD risk (Forabosco et al., 2013; Hickman et al., 2013; Keren-Shaul et al., 2017; Zhang et al., 2013)	↑	ns
	Arg1	M2 marker associated with resolving IL4 mediated Aβ plaque reduction (Gaikwad and Heneka, 2013)	ns	↓
	Cd11c	(CR4, ITGAX) Innate immune cell-specific integrin (Kamphuis et al., 2016; Keren-Shaul et al., 2017; Krasemann et al.,2017)	↑	ns
	CD68	Innate immune microglial lysosomal antigen upregulated in phagocytic cells (Zhao et al., 2016; Zotova et al., 2011)	↑	ns
Immunodysregulation, neurodegenerative associated microglial phenotype	Cd11b	(CR3, ITGAM) integrin receptor for complement opsonized Abeta, on innate immune cells, “M1” microglia activation marker, elevated in AD (Gaikwad and Heneka, 2013)	↓	ns
	iNOS*	Enzyme synthesizing NO, M1 microglia activation marker, elevated in AD (Gaikwad and Heneka, 2013)	↓	↓
	C1q	Highly elevated in aging and AD, first step in complement cascade and associated with synaptic stripping (Yasojima et al., 1999)	↓	ns
	CD33	Siglec receptor, tyrosine kinase signaling, elevated levels genetically implicated in AD (Bradshaw et al., 2013; Griciuc et al., 2013;Malik et al., 2015)	ns	↓
	mir155	Induces neurodegenerative microglia (Krasemann et al., 2017; Ma et al., 2017)	↓	–
	COX2*	pro-inflammatory enzyme, elevated (neuronal) in AD, affects excitoxicity (Chaudhry et al., 2010)	↓	↓
Microglial markers	TMEM119	Transmembrane protein, Microglia -specific marker, elevated in AD (Keren-Shaul et al., 2017; Satoh et al., 2016)	↓	ns
	P2ry12	Purinergic G-protein coupled receptor for ATP/ADP, on non-activated as well as activated microglia (Keren-Shaul et al., 2017)	↓	ns

^*Low and high dose have similar effects.