Table 1 Effects of innate and adaptive immune cells on Alzheimer’s disease progression

Cytokines

Effect of IL-1β on mouse primary neurons

Prostaglandin concentration increase, presynaptic glutamate release, postsynaptic N-methyl-d-aspartate receptor activation

Neurotoxicity, oxidative stress, and inflammation, leading to neuronal dysfunction and synapse loss

Mouse cells with prostaglandin-endoperoxide synthase 2 knock out

Zhou et al. [61]

Effect of IL-1β on mouse primary neurons exposed to Aβ oligomers

Mitochondrial dynamics disrupted, mitochondrial fission, fusion, and transport comprised

Increase of synapse loss and memory impairment

Mouse cells from hippocampus

Batista et al. [62]

Microglia

IBA1⁺ and CX3CR1^GFP cells

(immunohistochemistry and confocal microscopy)

Less ramified microglia when near Aβ plaques and compared to microglia from wild-type mice

Strong morphological changes in plaque-associated microglia

Plaque-distant microglia showed minor changes

3.5 to 5.5-month-old

TgCRND8^wt/wt; CXC3CR1^GFP/wt and TgCRND8^wt/tg; CXC3CR1^GFP/wt

Plescher et al. [63]

IBA1⁺ cells

(immunohistochemistry and confocal microscopy)

Dystrophic microglial morphologies, shortened cell arborization and cell soma size’s enlargement in the cerebral cortex

AD did not affect microglial density, but impaired morphology, with decreased ramified microglia in AD cases

Post-mortem samples of individuals with AD (44) and healthy controls (32)

Franco-Bocanegra et al. [64]

IBA1⁺ and P2Y12⁺ cells

(fluorescence-activated cell sorting and immunostaining)

SPP1 upregulation induced microglial phagocytic states in the hippocampus and enhanced synaptic engulfment by microglia

SPP1 is required for microglia to engulf synapses. Absence of Spp1 expression prevents synaptic loss suggesting crosstalk between perivascular cells and microglia

3- to 4-month-old APP/ SPP1^{tm1(tdTomato)Msasn} and APP^WT versus APP^NL−F mice

wild-type mice

De Schepper et al. [54]

Peripheral macrophages and monocytes

Plasma levels of monocyte chemoattractant protein-1 (MCP-1)

Highest MCP-1 concentration in AD patients compared to MCI and controls

MCP-1 dysregulated peripheral chemoattractant factors in AD contribute to inflammation

Individuals with AD (310), MCI (66) and healthy subjects (120). Age 70–80 years

Lee et al. [65]

Plasma levels of isolated monocytes/macrophages (CD14 + and CD16 −/+)

Different subsets of monocytes were found classical (CD14 + + CD16 −), intermediate (CD14 + + CD16 +) and non-classical (CD14 + CD16 + +). Intermediate subset was higher in MCI and AD groups

Hyperactivity of monocytes and macrophages during MCI contributes to AD progression. Circulating monocytes from AD patients produced significantly higher levels of free radicals compared to healthy subjects

Comparison among individuals with AD (14), subjective memory complaints (10), MCI (14), and healthy subjects (15)

Age range of 60–85 years

Munawara et al. [58]

T cells

T helper 1 and Th17 Aβ-reactive

IBA1⁺ cells (immunostaining); CD4⁺CD25⁺ and CD4⁺CD25⁻ flow cytometry; hippocampal transcriptional analysis

Th1 and Th17 Aβ-reactive facilitated Aβ deposition and suppressed T cells activity

APP/PS1/Aβ-Th1 mice showed an increased IBA1⁺ microglial cells density compared to controls. IBA1⁺ displayed a processes shrinkage and a more amoeboid morphology

Administration of Aβ reactive Th1 and Th17 cells to APP/PS1 mice resulted in an acceleration of memory impairment and systemic inflammation, an increase in amyloid burden, heightened microglia reactivity, and intensified neuroinflammation

6-month-old APP/PS1 mice transfused with cloned lines of Aβ-Th1 and Aβ-Th17 cells compared to untreated and age-matched wild-type mice

Machhi et al. [60]

β-site APP-cleaving enzyme 1 (BACE1)

(magnetic activated cell sorting of CD4 + T cells; flow cytometry analysis and western blotting for BACE1 expression)

BACE1 expression was higher in AD patients than healthy controls

CD4⁺ T cells in HUBC mice exhibited higher levels of BACE1 expression. CD4⁺ T cells with elevated BACE1 expression showed increased production of interleukin-2

Overexpression of BACE1 potentiates CD4⁺ T cell reactivity in patients with AD

29 AD patients, 27 healthy controls. Age 53–82 years. 4-month-old HUBC (human ubiquitin C promoter) mouse model compared age-matched wild-type and 5 × FAD mice

Dai et al. [66]

T-effector cells (immunohistochemistry; transcriptome analysis of the hippocampus)

CD8⁺ cells infiltrated the hippocampus, cortex and corpus callosum of APP/PS1 and even aged wild-type

CD8⁺ invade the AD brain and control the expression of genes related to neurons and synapses in APP-PS1 mice

3- to 26-month-old APP/PS1 compared to age-matched wild-type mice

Unger et al. [67]