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Table 2 Cellular infiltration in Alzheimer’s disease

From: The neuroimmune axis of 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]

  1. TCM central memory T cells, TEM effector memory T cells, TEMRA 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