Table 2.

Cellular infiltration in Alzheimer’s disease

Cell type	Model	Age	Disease-modifying role or correlation	Possible recruitment signal	References
Neutrophils	Human	Average age is 74.5 ± 10.4 for AD subjects	Unknown	Unknown	Zenaro et al., 2015 [207]
Neutrophils	5XFAD and 3x-Tg mice	4-month-old (5XFAD), 6-month-old (3xTg mice)	Depletion or inhibition of neutrophils trafficking reduced AD-like pathology and improved cognitive function	LFA-1 integrin	Zenaro et al., 2015 [207]
Monocytes	Appswe/PS1 mice	6–9-month-old	Reduced Aβ burden	Unknown	Malm et al., 2005 [208] Simard et al., 2006 [209]
Monocytes	Tg2576/TGF-β DNR mice	17–18-month-old	Reduced cerebral parenchymal and vascular β-amyloid deposits	TGF-β signaling	Town et al., 2008 [210]
Monocytes	APP/PS1 mice	6–7-month-old	Depletion of monocytes increased β-amyloid deposition	Aβ aggregates on blood vessels	Michaud et al., 2013 [211]
Monocytes	5XFAD mice	10-month-old	PD-1 blockade led to clearance of cerebral β-amyloid plaques and improved cognitive performance	PD-1/IFN-γ pathway	Baruch et al., 2016 [212]
CD8+ T cells	Human	16–81-year-old (Rogers, 1988), 56–96-year-old (Togo, 2002) for AD subjects	Likely have negative consequences for neuronal function and integrity	Unknown	Rogers et al., 1988 [213] Togo et al., 2002 [214]
CD8+ T cells	Human	Average age is 84.1 ± 3.6 for AD subjects	Unknown	Unknown	Merlini et al., 2018 [215]
CD8+ T cells	Human	72–96-year-old for AD subjects	Positive correlation of parenchymal CD8+ T cells with Braak stage	Unknown	Unger et al., 2020 [216]
CD8+ T cells	Human	Average age is 70.74 ± 7.01 for AD subjects	Positive correlation of peripheral TCM and TEM with cognition, and negative correlation of peripheral TEMRA with cognition	Unknown	Gate et al., 2020 [142]
T cells	APP/IFN-γ Tg mice	9-month-old	Clearance of Aβ	IFN-γ cytokine	Monsonego et al., 2006 [217]
CD4+ and CD8+ T cells	ArcAβ mice	12- and 22–24-month-old	No association with β-amyloid deposits	Aβ-induced endothelial cell activation	Ferretti et al., 2016 [218]
CD4+ and CD8+ T cells	APP/PS1 mice	6–7-month-old (Browne, 2013), 10-month-old (McManus, 2017), 18–19-month-old (Unger, 2020), 12–13-month-old (Gate, 2020)	Possible contribution of CD8+ T cells to neuronal dysfunction and modulation of synaptic plasticity	Unknown	Browne et al., 2013 [219] McManus et al., 2017 [220] Unger et al., 2020 [216] Gate et al., 2020 [142]
CD4+ and CD8+ T cells	5XFAD mice	12-month-old	TNF inhibitor treatment reduced CD4+ T cells in the brain, rescued impaired LTP, and decreased β-amyloid plaques	sTNF/TNFR1 signaling	MacPherson et al., 2017 [221] Shukla et al., 2019 [222]
Aβ-specific CD4+ TH1 cells	5XFAD mice	9-month-old	ICV-injected TH1 cells decreased β-amyloid plaques	Unknown	Mittal et al., 2019 [223]
Aβ-specific CD4+ TH1 and TH17 cells	APP/PS1 mice and Aβ42-induced rats	4–5-month-old (Machhi, 2021), 4-month-old (Zhang, 2013)	Teatment with TH1 and TH17 cells in APP/PS1 mice accelerated memory impairment and systemic inflammation, increased amyloid burden, activated microglia, and exacerbated neuroinflammation; TH17 cells mediated neuroinflammation and neurodegeneration in Aβ42-induced rats	Unknown	Machhi et al., 2021 [224] Zhang et al., 2013 [225]
CD4+ T cells	3xTg mice	6–9-month-old	$\alpha$4 blockade reduced Aβ load, Tau hyperphosphorylation and memory decline	$\alpha$4β1 integrin-VCAM-1 signaling	Pietronigro et al., 2019 [226]
Treg cells	5XFAD mice	10-month-old	PD-1 blockade led to clearance of cerebral β-amyloid plaques and improved cognitive performance	PD-1/IFN-γ pathway	Baruch et al., 2016 [227]
Treg cells	APP/PS1 mice	4–7-month-old	Depletion of Treg cells accelerated cognitive deficits and amplification of Treg cells by IL-2 treatment increased plaque-associated microglia, and improved cognitive functions	Unknown	Dansokho et al., 2016 [228]
B cells	3xTg mice	14–16-month-old	Depletion of B cells reduced β-amyloid plaque burden and microglial activation	Unknown	Kim et al., 2021 [229]

T_CM central memory T cells, T_EM effector memory T cells, T_EMRA terminally differentiated memory T cells, sTNF soluble tumor necrosis factor, TNFR1 tumor necrosis factor receptor 1, TGF-β transforming growth factor beta, PD-1 programmed death-1, IFN-γ interferon gamma, LFA-1 lymphocyte function-associated antigen 1, ICV intracerebroventricularly, LTP long-term potentiation