Table 2.

Main evidence coming from animal studies. 3,6-DT 3,6-Dithiothalidomide; Aβ amyloid beta; AD Alzheimer’s disease; APP amyloid precursor protein; ELISA Enzyme Linked Immunosorbent Assay; IL interleukin; NaHS hydrogen sulfide; PS1 presenilin 1; RT-PCR reverse transcription polymerase chain reaction; tg transgenic; TfRMAb transferrin receptor antibody; TNF-α tumor necrosis factor α; TNFR TNF-α tumor necrosis factor α receptor.

Reference	Animal Model	Compound	Methods	Main Findings
Seabrook et al., 2006 [114]	APP-tg mice	Minocycline	ELISA and memory and cognitive testing	Increasing in Aβ deposition but cognitive performance improved. Administration post-Aβ deposition suppressed microglial activation without impacting in Aβ levels or cognitive function.
Biscaro et al., 2012 [115]	APP/PS1 mice	Minocycline	ELISA, cognitive testing and memory and cognitive testing	minocycline treatment increased the survival of dentate granule cells
Chavant et al., 2010 [116]	APP-tg mice	Imipramine	Western blottings, ELISA, cognitive testing and memory and cognitive testing	reduce elevated Aβ levels
Shi et al., 2011 [131]	APP/PS1 mice	Infliximab	Immunohistochemistry	Reduction in TNF-α levels, Aβ plaques and decreased pTau protein. An increase in CD11c-positive dendritic cells.
Xuan et al., 2012 [118]	Wistar rats	NaHS	RT-PCR, analysis, memory and cognitive testing and working memory testing.	NaHS mitigates the presence of Aβ1-40 demonstrating a neuroprotective role and a reduction in the expression of TNF-α and IL-1 β levels.
Gabbita et al., 2012 [122]	3xTg-AD mice	Thalidomide and its analog 3,6-DT	Immunohistochemistry, RT-PCR analysis, and memory and cognitive testing.	An enhancement in working memory performance. 3,6-DT prevents cognitive impairment.
Belarbi et al., 2012 [123]	AD mice	3,6-DT	Immunohistochemistry, and cognitive testing.	The treatment successfully normalized TNF-α levels, although IL-1β remained elevated.
Tweedie et al., 2012 [124]	3xTg-AD mice	3,6-DT	RT-PCR, Immunohistochemistry, and cognitive testing.	Decreased levels of pTau protein, Aβ peptide, and Aβ plaque numbers and memory improvement.
Bomfim et al., 2012 [125]	APP/PS1 mice	Exendin-4 along with Infliximab	Immunohistochemistry, memory and cognitive testing.	Association between impaired brain insulin levels and cognitive impairments.
X.-H. Li et al., 2013 [130]	Wistar rats	Atorvastatin	Immunohistochemistry, Memory and working memory testing.	Assessment of decreasing in neuroinflammatory cytokines, including IL-1β, IL-6 and TNF-α levels.
Kübra Elçioğlu et al., 2015 [133]	Sprague–Dawley mice	Thalidomide, Etanercept and Infliximab	Memory and cognitive testing.	Results indicated that all treatment groups exhibited preventive effects on learning and memory deficits, in particular the thalidomide group.
Park et al., 2019 [134]	Aβ1-40 mice	Adalimumab	Immunohistochemistry, Memory and working memory testing.	Adalimumab treatment not only reduced neuronal damage but also mitigated neuroinflammation.
Y. Li et al., 2022 [135]	3xTg-AD	Etanercept	Immunohistochemistry, Memory and working memory testing.	Etanercept treatment significantly enhanced spatial memory, long-term memory, and working memory and lowered cytokine levels in AD mice.
Ou et al., 2022 [138]	APP/PS1 mice	TfRMAb-TNFR	Immunohistochemistry, Memory and working memory testing.	TfRMAb-TNFR exerted protective effects, effectively reducing the levels of Aβ plaques.