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. 2023 May 30;4(6):1375–1388. doi: 10.1016/j.fmre.2023.05.008

Table 1.

The roles of MIF in AD.

Authors Study design Results
Popp et al. 2009 [25] AD patients: mean age (years) = 69.77, gender (m/f) = 12/19
MCI patients: mean age (years) = 67.04, gender (m/f) = 20/8
Control: mean age (years) = 67.05, gender (m/f) = 12/7
CSF MIF increased positively with TNF-α production.
Bacher et al.2010 [26] AD patients: mean age (years) = 66.71, gender (m/f) = 5/2
Control: mean age (years) = 66.57, gender (m/f) = 5/2
APP 23 transgenic mouse
CSF MIF increased.
MIF in microglial cells was associated with Aβ plaques.
ISO-1 inhibited Aβ-induced neurotoxic in SHSY and BV-2 cells.
Zhang et al. 2019 [17] AD patients: mean age (years) = 69.4, gender (m/f) = 14/14
MCI patients: mean age (years) = 68.9, gender (m/f) = 4/6
Control: mean age (years) = 61.2, gender (m/f) = 14/16
AD patients brain: mean age (years) = 68.4, gender (m/f) = 3/2
Control brain: mean age (years) = 48.4, gender (m/f) = 4/1
APP23/MIF+/− mice
MIF served as a defense mechanism and a biomarker of AD.
MIF upregulated both in CSF and brain tissue.
MIF deficiency affected cognitive functions in AD mice.
MIF colocalized and interacted with Aβ oligomers.
MIF overexpression inhibited Aβ-induced cytotoxicity.
Oikonomidi et al. 2017 [32] CI: mean age (years) = 74.16, gender (m/f) = 44/53
Control: mean age (years) = 66.38, gender (m/f) = 16/36
CSF MIF levels were higher in CI with AD which associated with higher CSF tau and p-tau and lower CSF Aβ1–42, independently predicted cognitive decline.
Nasiri et al. 2020 [27] AD patients: mean age (years) = 69.7, gender(m/f) = 10/9
Control: mean age (years) = 70.5, gender (m/f) = 5/9
6-month-old male C57BL/6 or MIF-KO mice subjected to ICV-STZ
CSF MIF increased and positively associated with tau, p-tau and negative associated with Aβ1–42.
ISO-1 improved the STZ-induced memory impairment in contextual by reducing cytokine production.
Flex et al. 2014 [34] AD patients: mean age (years) = 76.6, gender (m/f) = 188/353
Control: mean age (years) = 76.7, gender (m/f) = 268/445
No significant difference in the distribution of the CRP, MIF, and TNF-gene polymorphism.
Carlred et al. 2016 [29] 18-month-old transgenic mice (3 male, 1 female) with the Arctic (E693G) and Swedish (K670N, M671L) mutations (tgArcSwe) of human APP MIF colocalized with activated microglia (Iba1) to the Aβ positive deposits in the hippocampal region.
Li et al. 2015 [30] APP/PS1 transgenic mice were mated with MIF−/− mice
3-6-month-old female WT and MIF−/− mice subjected to ICV-STZ
Primary astrocyte were treated with high glucose to mimic STZ function
ICV-STZ increased astrocyte activation and MIF expression in the hippocampus.
MIF deficiency or ISO-1 attenuated tau hyperphosphorylation and astrocyte activation.
Liang et al. 2018 [31] 4-week-old male mice received D-galactose- and AICI3 for 90 d to induced AD model, then administrated Fufang Danshen for 14 d.
SH-SY5Y cells
Fufang Danshen suppressed MIF induced apoptosis in SH-SY5Y cells by decreasing Bad levels via Akt and IKKα/β signals.
Fufang Danshen downregulated the levels of MIF, Bad and INF-γ in AD mouse model.