The dual roles of cytokines in Alzheimer’s disease: update on interleukins, TNF-α, TGF-β and IFN-γ

Zheng, Cong; Zhou, Xin-Wen; Wang, Jian-Zhi

doi:10.1186/s40035-016-0054-4

Translational Neurodegeneration

Table 1 Cytokine polymorphisms and levels in serum or CSF

From: The dual roles of cytokines in Alzheimer’s disease: update on interleukins, TNF-α, TGF-β and IFN-γ

Cytokines^a		Levels^b				Polymorphisms/haplotypes	Corresponding cytokine expression^c	Results^d	Methods	Ref.
		MCI		AD
		Plasma/serum	CSF	Plasma/serum	CSF
IL-1 family [144]	IL-1α	=	\	= or ↓	\	-889 C/T (rs1800587)	T: ↑	* ↑ in EOAD	Meta-analysis	[145]
								No * in LOAD.	Meta-analysis	[145]
								* ↑ in Caucasians	Meta-analysis	[14]
								No * in Asians.	Meta-analysis	[14]
	IL-1β	↑	=	↑or =	= or ↑	-511 C/T (rs16944)	?	no*	Meta-analysis	[15]
						-31 T/C (rs1143627)	C: ?	*↓ in Italians	Case–control	[25]
						−511C/−31 T/IL1RN2	?	*↓ in elderly group of Brazilians	Case–control	[23]
						−511C/−31C/IL1RN1	?	* ↑ in Brazilians	Case–control	[23]
						+3953 C/T (rs1143634)	T: ↑	* ↑ in non-Asians	Meta-analysis	[15], [14]
						Exon 5 E1/E2	\	No* in Taiwan population	Case–control	[146]
	IL-1ra	\	\	-	↓ [139]	Intron 2 I/II/IV	\	No* in Taiwan population	Case–control	[146]
	IL-18 [71]	=	\	= or ↑	↑	-607 A/C (rs1946518)	C: ↑	* ↑ in LOAD of Han Chinese.	Case–control	[20]
						-607 A/C (rs1946518)	C: ↑	*↑↑ in ApoE ε4 carrier.
						-137 C/G (rs187238)	G: ↑	*↑↑ in ApoE ε4 carrier.
						-607 C or -137 G	↑	* ↑ in LOAD of Han Chinese.
	IL-33 [147]	\	\	\	\	rs11792633 C/T	T: ↑	*↓ in non-ApoE ε4 carrier in both Caucasians and Han Chinese.	Case–control	[19],[148]
	IL-4 [149]	\	\	\	\	-1098 T/G (rs2243248)	G: Possibly ↓	*↑ in Han Chinese	Case–control	[150]
						-1098 T/G (rs2243248)	T: Possibly ↓	*↑ in Caucasians		[151]
						-590 C/T (rs2243250)	C: ↓	*↑ in Han Chinese and Caucasians		[150], [151]
IL-6 family	IL-6 [152, 153]	=	\	↑or =	= or ↑	-174 G/C (rs1800795)	C: ↓	↓ in Asians, No in Caucasians.	Meta-analysis	[10].
						-174 G/C (rs1800795)	C: ↓	*↓ in Italians.	Case–control	[25]
						-572 C/G (rs1800796)	C: ?	*↑ in ApoE ε4 carriers.	Case–control	[16]
	IL-11 [154]	=	\	= or ↑	↑	\	\	\	\	\
	IL-10 [155, 156]	=	↑	= or ↑	=	-1082 A/G (rs1800896)	A: ?	↑ in Caucasians, No in Asians.	Meta- analysis	[11]
						-1082 A/G (rs1800896)	G: ↑	↓ in Caucasians	Meta- analysis	[22]
						-819 T/C (rs1800871)	?	no *
						-592 A/C (rs1800872)	?	no *
						-1082G/-819C/-592C	?	↓
IL-12 family [157]	IL-12A	=	\	=	=	rs2243115 T/G	G: ↓	*↓ in LOAD in ApoE ε4 carrier of Northern Han Chinese	Case–control	[17]
	IL-12A	=	\	=	=	rs568408 G/A	A: ↓	*↓ in LOAD of Northern Han Chinese
	IL-12B	=	\	=	=	rs3212227 A/C	C: ↓	*↓ in LOAD of Northern Han Chinese
	IL-23	\	\	\	\	rs10889677 A/C (L-23R)	C: ↓	*↓ risk in Northern Han Chinese.	Case–control	[18]
	IL-23	\	\	\	\	rs1884444 T/G (IL-23R)	G: ↓	*↑ in ApoE ε4 carrier of Northern Han Chinese.	Case–control	[18]
	IL-15 [158]	\	\	=	=[159]	\	\	\	\	\
	IL-16 [160]	\	\	\	\	rs4072111 C/T	T: ?	*↓ in LOAD of Iranians.	Case–control	[161]
	IL-17 [162]	\	\	\	\	\	\	\	\	\
	TNF-α [163]	= or ↑	↓	= or ↑ or ↓	= or ↑ or ↓	-308 G/A (rs1800629)	A: ↑	*↑ in East Asian	Meta-analysis	[12], [13]
								*↓ in Northern European population.	Meta-analysis	[12], [13]
								No* in Italians	Case–control	[25]
	TGF-β [164]	\	↓	↑ or ↓ or =	↑ or ↓ or =	\	\	\	\	\
	IFN-γ [165]	\	\	=	=	-874 T/A (rs62559044)	A: ↓	*↑ in fast progressing AD	Case–control	[27]

Abbreviation: IL-1 ra IL-1 receptor antagonist, EOAD early-onset Alzheimer’s disease, LOAD late-onset Alzheimer’s disease
^aEach cytokine or cytokine family was supplemented with a latest review for detailed information of physiological parameters
^b↑: up-regulated, ↓: down-regulated, =: no change, \: no data. Unless otherwise noted, all the data of cytokine levels is from Brosseron et al. 2014 [8]
^c↑: enhance the cytokine expression, ↓: attenuate the cytokine expression, ?: unknown yet
^d*: significant, ↑: higher risk of AD onset, ↓: lower risk of AD onset

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