The immune response within Alzheimer’s disease: from the lense of peripheral monocyte-derived macrophages

Abstract

Alzheimer’s disease (AD) is the most significant form of dementia characterized by neurodegeneration and higher-order cognitive decline affecting over 6.9 million Americans age 65 and older. Emerging evidence for AD pathogenesis has expanded mechanistic investigation from focusing on the central nervous system (CNS), to including the peripheral immune system. Microglia in CNS and their counterpart peripheral monocyte-derived macrophages (MDMs) share fundamental functions as innate cells that contribute to the inflammatory response, phagocytosis of debris, and tissue repair after injury. As recently recognized in AD pathogenesis, MDMs have distinct origins and respond differently to environmental cues relative to microglia, presenting unique potentials for therapeutic targeting outside of the blood-brain barrier. In this review, we will diverge from the previously highlighted primary immune regulator in the CNS, the microglia, to explore the significance of MDMs as a peripheral-origin contributor to the pathogenesis of AD.

1. Introduction

Alzheimer’s disease (AD) is a devastating neurodegenerative disease without a cure at this time. Being the most common cause of dementia and a leading cause of death in the United States, AD affects an estimated 6.9 million Americans aged 65 and older in 2024 (Alzheimers Dement., 2024). As the population ages, the number of people suffering from AD is also expected to rise. AD is characterized by brain atrophy, the deposition of amyloid- β (Aβ) plaques, neurofibrillary tangles (NFTs), composed of tau protein, and the loss of neurons and synapses (Fu et al., 2024; Iyer et al., 2025). Previous investigations centered their studies on the impact of microglia on amyloid deposits containing Aβ fibrils and neuronal cell death, the major contributors to disease progression. Although there is an urgent need to address the onset and progress of AD, limited treatments are available to aid in physiological symptoms, and none which can slow the progression of the disease. This review will focus on peripheral monocyte-derived macrophages (MDMs) for their contribution to the disease and the potential to deliver new therapeutic designs.

Myeloid cells are key components in immunity with a wide presence throughout the body at various developmental stages to guard against foreign invasion and maintain tissue homeostasis. Importantly, myeloid cells are critical to the development of AD and age-related degeneration, specifically when their functions are altered by normal aging processes and contribute to Aβ plaque accumulation, or they elicit a pro-inflammatory response to the excess of Aβ plaques which promotes AD progression (Yan et al., 2022; Cugurra et al., 2021; Villacampa and Heneka, 2020; Martin et al., 2017; Herisson et al., 2018; Geissmann et al., 2010; Juul-Madsen et al., 2024; Mildner et al., 2011). Two major myeloid lineages in CNS can directly contribute to AD: resident microglia that derive from yolk sac progenitors during embryogenesis and monocyte-derived macrophages (MDMs) arising from bone marrow progenitors infiltrating into the CNS during brain injury (Geissmann et al., 2010; Mildner et al., 2011; Prinz and Priller, 2014). Microglia, the resident macrophages in the CNS, contribute to immune responses, maintain brain homeostasis, and support the brain in its development and repair mechanisms. As specialized cells, it is logical to expect their function in the immune response efforts during the degenerative process of AD’s pathogenesis (Fu et al., 2024). On the other hand, MDMs infiltrate into the CNS from the circulation during injury upon chemoattractant recruitment and execute professional scavenging and inflammatory duties, meaning bearing epigenomic notes from system physiological cues such as aging and chronic diseases (Yan et al., 2022; Cugurra et al., 2021; Martin et al., 2017; Silvin et al., 2022). Interestingly, some studies compared the Aβ plaque clearance capacity of these two myeloid cells using chimeric mouse models or microglial ablation experiments and observed more efficient Aβ plaque elimination capability of MDMs relative to microglia, suggesting their direct and potent impact on AD pathogenesis and progress (Mildner et al., 2011; Simard et al., 2006; Grathwohl et al., 2009; Krabbe et al., 2013). Given the peripheral origin, MDMs could also provide a feasible value to deliver therapeutic medications to target AD enclosed by the blood-brain barrier (BBB) (Boillee, 2022; Mucke, 2009; Zenaro et al., 2015).

2. Origin and differentiation of MDMs

The innate immune system has been well established as a contributor to the development and progression of AD. However, most research focused on microglia for their essential role in CNS normal function and direct contributions or mitigation of neuroinflammation (Villacampa and Heneka, 2020; Martin et al., 2017; Mildner et al., 2011; Boillee, 2022; Prinz and Priller, 2014; Hansen et al., 2018; Leng and Edison, 2021; Morgan et al., 2005). The peripheral immune system remains highly debated for its relevance to AD. Recruitment of circulating immune cells in response to CNS damage involves more cells than microglia, such as MDMs and dendritic cells, which have only recently been acknowledged. It is recognized that MDMs directly contribute to AD pathogenesis (Yan et al., 2022; Juul-Madsen et al., 2024; Mildner et al., 2011; Simard et al., 2006), but it is currently unclear how and to what degree they contribute to the onset and development of the disease.

MDMs originate from bone marrow derived monocytes, which enter circulation and can infiltrate the CNS in response to injury or inflammation (Geissmann et al., 2010; Prinz and Priller, 2014; Tian et al., 2025). Upon entering circulation, these cells are vital to innate immunity as they respond to tissue injury and inflammation and differentiate into tissue-resident macrophages, including MDMs in the CNS (Gonul et al., 2025; Zuroff et al., 2017; Naert and Rivest, 2013). Monocytic differentiation is regulated by environmental cues such as cytokines and chemokines, which drive their transformation into macrophages upon migration into tissues (Herisson et al., 2018; Silvin et al., 2023; Podleśny-Drabiniok et al., 2025). Unlike yolk sac-derived microglia, MDMs are continuously replenished from the bloodstream, allowing them to respond dynamically to AD’s neuroinflammatory environment (Cugurra et al., 2021; Herisson et al., 2018). Studies have also shown that skull bone marrow may be a direct source for MDMs entering the CNS through skull-meningeal connections (Cugurra et al., 2021; Herisson et al., 2018; Mazzitelli et al., 2022). Importantly, exciting studies using in vivo labeling and imaging tracing suggested that macrophages can be directly recruited from the skull bone marrow through skull-meninges connections and contribute to AD and other neurological disorders (Herisson et al., 2018; Kolabas et al., 2023; Pulous et al., 2022). These discoveries underscore the involvement of MDMs in AD with a significantly more direct impact than previously known.

MDMs display remarkable plasticity, which enables them to adopt various phenotypes depending on the tissue environment and the specific signals encountered (Martin et al., 2017; Savinetti et al., 2021; Zhao, 2020; Silvin et al., 2022; Famenini et al., 2017). In the CNS, MDMs contribute significantly during pathological conditions such as neuroinflammation or injury (Yan et al., 2022; Mildner et al., 2011; Boillee, 2022; Zhao et al., 2020). Recent studies have shown that MDMs exhibit distinct gene expression patterns compared to resident microglia which is critical when examining their roles in neurodegeneration, particularly in AD (Yan et al., 2022; Bastos et al., 2025; Lee et al., 2025; El Khoury et al., 2007; Thome et al., 2018). While microglia largely originate from yolk sac progenitors, MDMs are continuously replenished from the bone marrow and circulate through the bloodstream, responding to inflammatory signals and differentiating upon entry into the CNS (Prinz and Priller, 2014; Silvin et al., 2022).

2.1. Recruitment of MDMs

The deterioration of the BBB in AD facilitates the entry of peripheral immune cells, particularly MDMs, into the CNS. Under normal physiological conditions, the BBB tightly regulates the trafficking of cells between the bloodstream and the brain, but in AD, this barrier becomes increasingly permeable (Gu et al., 2025; Tian et al., 2025). This breakdown is partially driven by chronic inflammation, oxidative stress, and Aβ deposition (Boillee, 2022; Zuroff et al., 2017). MDMs transmigrate across the compromised BBB via interactions with endothelial adhesion molecules, such as ICAM-1 and VCAM-1 which are upregulated during neuroinflammation (Juul-Madsen et al., 2024; Zenaro et al., 2015; Zhao et al., 2020; Silvin et al., 2022). These adhesion molecules help tether MDMs to the endothelium, where they can subsequently migrate into the brain parenchyma. Once inside the CNS, MDMs may either adopt neuroprotective roles by clearing Aβ deposits or contribute to ongoing neuroinflammation, depending on their polarization states (Prinz and Priller, 2014; Famenini et al., 2017) (Fig. 1). In addition, perivascular macrophages (PVMs), which originate from the yolk sac like microglia, are important for immune surveillance and have been implicated in Aβ clearance. While CCR2 signaling facilitates MDM recruitment to the CNS, its specific role in PVM-mediated Aβ transport across the BB remains to be determined (Yan et al., 2022; Cugurra et al., 2021; Martin et al., 2017; Mildner et al., 2011; Boillee, 2022; Prinz and Priller, 2014; Zhao et al., 2020; Lin et al., 2022; Silvin et al., 2023; Munawara et al., 2021; El Khoury et al., 2007; Naert and Rivest, 2013). The progressive loss of BBB integrity in AD creates a permissive environment for MDM infiltration, further complicating the disease’s progression.

Fig. 1.

Interaction of Peripheral Monocytes and the CNS in Alzheimer’s Disease.

This figure illustrates the recruitment of peripheral monocytes into the central nervous system (CNS) across the blood-brain barrier (BBB). Once infiltrated, monocytes differentiate into monocyte-derived macrophages (MDMs) in response to neuroinflammatory signals, including amyloid plaques. These MDMs interact with neurons, microglia, and astrocytes, playing diverse roles in Alzheimer’s Disease (AD) pathology. Their contributions range from neuroprotection and debris clearance to potential exacerbation of neuroinflammation, highlighting their dual-edged role within the CNS immune landscape.

Chemokine signaling is critical in the recruitment on MDMs to sites of neuroinflammation in AD. While CCR2 has been well studied for its role in recruiting monocytes to the CNS, other chemokine receptors and ligands, such as CX3CR1, CCL2, and CCL5 are also significant (Martin et al., 2017; Zhao et al., 2020; Savinetti et al., 2021; Silvin, 2022; Silvin et al., 2023). CX3CR1, which is expressed on MDMs and microglia, binds to the chemokine CX3CL1 (fractalkine), a molecule that is highly expressed in neurons. This interaction regulates the movement of immune cells into the CNS and modulates their phagocytic activity (Martin et al., 2017; Leng and Edison, 2021; Zhao et al., 2020; Silvin et al., 2023). Additionally, CCL2 and CCL5 are produced by inflamed CNS tissues and play a significant role in the recruitment of circulating monocytes during neurodegenerative processes (Cugurra et al., 2021; Leng and Edison, 2021; Savinetti et al., 2021). Dysregulation of these pathways could impair the ability of MDMs to respond to Aβ accumulation, leading to chronic inflammation and worsening pathology (Cugurra et al., 2021; Nie et al., 2025). Understanding chemokine signaling pathways relative to AD may reveal new therapeutic strategies to manage MDM recruitment and function.

Chronic inflammation is a hallmark of AD and is central to the recruitment of MDMs to sites of pathology. Elevated levels of TNF-α, IL-1β, and IL-6 are observed in both the periphery and the CNS during AD, which creates chemotactic gradients to draw peripheral immune cells into the brain (Zenaro et al., 2015; Silvin et al., 2022; Munawara et al., 2021; Fani Maleki and Rivest, 2019). Systemic inflammation, whether triggered by infection, injury, or age-related immune dysregulation, can enhance the recruitment of MDMs to the CNS by increasing the production of chemokines like CCL2 and the expression of endothelial adhesion molecules (Cugurra et al., 2021; Zhao et al., 2020). Once recruited, these MDMs are involved in Aβ clearance, but their phagocytic capacity appears to decline as the disease progresses (Juul-Madsen et al., 2024; Fiala et al., 2005; Gonul et al., 2025). The inflammatory milieu within the AD brain may shift MDMs toward a more pro-inflammatory phenotype, exacerbating neurodegeneration. In a recent study with human subjects, an anti-TNF-α antibody, called Enbrel, was administered to rheumatoid arthritis patients and reduced the risk of AD by 64 % (Chou et al., 2016). However, in the Phase II of the trial with established AD, the results showed only a trend toward improvement but not statistically significant (Butchart et al., 2015). Administration of anti-TNF-α in the early stages of neurodegeneration could slow down the recruitment of cells exacerbating neurodegeneration. The balance between the beneficial and harmful roles of MDMs in the context of AD-related inflammation is a critical underpinning in harnessing their therapeutic potential.

2.2. Function of MDMs

MDMs are phagocytic cells with significant roles in clearing debris and misfolded proteins like Aβ. Early in AD, MDMs may help reduce Aβ plaque burden by engulfing and degrading plaques, potentially slowing disease progression. MDMs’ phenotypic plasticity allows them to adopt either pro-inflammatory or anti-inflammatory states, or a multitude of intermediate stages which has been suggested by recent research, based on their local environment (Martin et al., 2017; Silvin et al., 2022) (Fig. 2). Upon exposure to an inflammatory trigger, such as infection, they promote leukocyte recruitment to the infection site by secreting chemokines and cytokines, activate the vascular endothelium via TNFα to facilitate leukocyte entry, and stimulate leukocyte activation—including NK cells, T cells, and B cells—through cytokines like TNFα, IL-6, IL-12, and IL-1β (Morgan et al., 2005; Fani Maleki and Rivest, 2019). In efforts of resolution, MDMs can secrete anti-inflammatory factors such as IL-10 and TGF-β, clear dead cells, and promote the clearance of amyloid plaques (Morgan et al., 2005; Munawara et al., 2021). Pro-inflammatory MDMs can activate cytokines (e.g., TNF- α, IL-1β) which can lead to excessive recruitment of leukocytes and further the disease pathogenesis (Podleśny-Drabiniok et al., 2025; Fani Maleki and Rivest, 2019). Fiala et al. studied AD mouse models and showed that MDMs could clear Aβ to prevent neuronal death in an anti-inflammatory fashion by favoring phagocytosis while maintaining their pro-inflammatory characteristics as cytokines were observed being expressed (Famenini et al., 2017; Munawara et al., 2021; Fiala et al., 2005). However, as AD progresses, MDMs often adopt a more neurotoxic, pro-inflammatory phenotype that contributes to chronic inflammation and exacerbates neuronal damage.

Fig. 2.

Function of MDMs as a spectrum of inflammatory roles.

Monocyte-derived macrophages (MDMs) exhibit phenotypic plasticity, enabling them to dynamically adapt to their local microenvironment. MDMs can polarize toward pro-inflammatory or anti-inflammatory states depending on the signals present, as well as adopt intermediate or hybrid phenotypes that manifest a spectrum of functional states. This plasticity is critical to their role in neuroinflammation, amyloid clearance, and AD progression or prevention based on the context of their environment.

Functionally, MDMs are highly phagocytic and are pivotal in clearing cellular debris, pathogens, and misfolded proteins. In neurodegenerative conditions, such as AD, MDMs actively participate in clearing amyloid plaques and damaged neurons (Yan et al., 2022; Simard et al., 2006). The recruitment of MDMs to areas of Aβ accumulation positions them as potential mediators of Aβ clearance (Juul-Madsen et al., 2024; Zuroff et al., 2017). Through phagocytosis, MDMs are known to clear cell debris or dead cells, which could be applied to Aβ aggregates in which they could engulf or degrade them (Famenini et al., 2017; Fiala et al., 2005; Michaud et al., 2013). Their efficiency in this role is a function that could decline with disease progression, raising the question of whether these cells maintain a pro or anti-inflammatory phenotype (Abellanas et al., 2025; Tian et al., 2025; Saresella et al., 2014). Normal conditions grant macrophages the ability to phagocytose and clear Aβ, but in patients with AD, this ability is impaired (Fiala et al., 2005; Gonul et al., 2025). One study in 2021 compared the phagocytic capabilities on monocytes and microglia between healthy elderly patients and mild cognitive impairment (MCI) elderly patients by measuring their uptake of fluorescent Aβ (Munawara et al., 2021). Monocytes from healthy individuals exhibited significantly higher baseline phagocytosis of Aβ than microglia, and all cell types showed increased phagocytic capacity when cultured with beta-hydroxybutyrate (BHB), an inflammasome inhibitor (Munawara et al., 2021). However, the experimental design of this study used a microglial cell line rather than primary human microglia, which may limit the physiological relevance of the comparison, and future studies should validate these findings using primary human microglia to better reflect in vivo conditions. Interestingly, LPS stimulation, typically enhancing immune activity via TLR4, did not boost phagocytosis in glucose media but did enhance phagocytic capacity in BHB media (Silvin et al., 2022; Munawara et al., 2021; Fiala et al., 2005; Gonul et al., 2025). Healthy elderly monocytes were the most effective at phagocytosis, while MCI monocytes displayed reduced capacity, which was improved by BHB. This suggests a potential role for BHB in boosting phagocytosis, particularly in compromised cells (Munawara et al., 2021; Gonul et al., 2025).

2.3. MDMs’ interplay with microglia

Although MDMs and microglia share myeloid origins and overlapping functions, they exhibit distinct transcriptional and surface marker profiles that are critical for their identification and functional interpretation. Microglia express markers such as P2RY12, TMEM119, SALL1, FCRLS, HEXB, and CD45^lo, while MDMs are typically characterized by high expression of CD45, CD44, CD169, and CD206 (Martin et al., 2017; Geissmann et al., 2010; Mildner et al., 2011; Hansen et al., 2018; Zhao et al., 2020; Silvin et al., 2022). Both populations additionally express overlapping markers including CD11b, CD68, CX3CR1, F4/80, and IBA1, which complicates their distinction in inflamed tissue (Geissmann et al., 2010; Mildner et al., 2011; Zhao et al., 2020). These differences are critical for accurately interpreting their respective roles in AD pathogenesis (Table 1).

Table 1.

Cell surface markers for MDMs and microglia.

Marker	Microglia	MDMs	Shared	Notes
P2RY12	High	Negative		Microglia-specific, downregulated during inflammation
TMEM119	High	Negative		Homeostatic microglia marker
FCRLS	High	Negative		Microglia-enriched gene
HEXB	High	Negative		Stable microglial marker
SALL1	High	Negative		Microglia transcription factor
CD45	Low (CD45^lo)	High (CD45hi)		Used in flow cytometry to distinguish CNS-resident vs infiltrating
CD206	Low/intermediate	High (CD206hi)		Marker of alternatively activated macrophages
CD44	Negative/Low	High		Involved in cell adhesion and migration
CD169	Negative	Positive		Associated with perivascular macrophages (PVMs)
CD11b	Positive	Positive	Yes	General myeloid/macrophage marker
CD68	Positive	Positive	Yes	Lysosomal/phagocytic marker
CX3CR1	High	Variable	Yes	Expressed by both; higher in homeostatic microglia
F4/80	Positive	Positive	Yes (mouse-specific)	Mouse macrophage marker
IBA1	Positive	Positive	Yes	Actin-binding protein, a general macrophage marker

Markers genes can differentiate microglia from MDMs in the central nervous system at basal and disease states. Genes are categorized based on their expression in microglia and MDMs, as well as if they are existing in a shared manner.

MDMs secrete factors including IL-1β, TNF- α, and CCL2 that can activate microglia, driving them into a pro-inflammatory state (Munawara et al., 2021; Chou et al., 2016; Butchart et al., 2015). Contrarily, microglia can produce molecules such as TGF- β and IL-10, which may influence the polarization and functional states of MDMs, promoting either a protective or pathogenic phenotype (Morgan et al., 2005). Using two established transgenic mouse models of AD–TgAPP/PS1, which coexpresses mutant human amyloid precursor protein (APP) and presenilin-1 (PS1), and TgAPP/PS1dE9, which expresses human APP along with a deletion mutant of PS1 (PS1dE9) to promote amyloid beta accumulation–an increase in IL-1β production was observed in 8-month-old TgAPP/PS1 mice and 10-month-old TgAPP/PS1dE9 mice compared to the wild type littermates (Martin et al., 2017). A similar pattern was found when looking at TNF-α levels in MDM of the transgenic mouse models compared to the wild type mice (Morgan et al., 2005). The changes in cytokine production occur in response to Aβ pathology, as no significant alterations in cytokine levels were observed during normal aging. This suggests that crosstalk between immune cells may be necessary to drive the observed increase in cytokine production, and perhaps in other factors as well.

MDMs can influence microglial behavior via direct cell-cell contact through receptors such as TREM2 (triggering receptor expressed on myeloid cells 2) and SIRPα (signal regulatory protein alpha), which regulate phagocytosis and immune responses (Abellanas et al., 2025; Hansen et al., 2018; Leng and Edison, 2021; Silvin et al., 2022; Jocher et al., 2025; Medd, 2025). The presence of MDMs may enhance or compete with microglia to clear debris such as Aβ plaques depending on their respective activation states (Mildner et al., 2011; Simard et al., 2006; Grathwohl et al., 2009; Krabbe et al., 2013; Zuroff et al., 2017). This interaction between MDMs and microglia is dynamic and may evolve with disease progression, shifting the balance between presumed beneficial and harmful immune responses.

The crosstalk between MDMs and microglia has significant implications for both neuroinflammation and neurodegeneration in AD. In the early stages of the disease, MDMs and microglia may collaborate in clearing Aβ plaques and maintaining homeostasis in the brain (Mildner et al., 2011; Simard et al., 2006; Krabbe et al., 2013; Zuroff et al., 2017). Through complementary roles in phagocytosis, these cells could limit the buildup of toxic protein aggregates and protect neurons from the harmful effects of Aβ (Gonul et al., 2025; Michaud et al., 2013; Saresella et al., 2014).

However, as the disease progresses, the interaction between MDMs and microglia can exacerbate neuroinflammation. Pro-inflammatory cytokines secreted by both cell types, including IL-1β, IL-6, and TNF-α, contribute to a chronic inflammatory environment that disrupts synaptic functions, impairs neurogenesis, and accelerates neuronal loss (Morgan et al., 2005; Sanfilippo et al., 2025). Microglia may adopt a “primed” state in response to signals from MDMs, provoking an exaggerated response to subsequent stimuli. This chronic activation can trigger the release of reactive oxygen species (ROS) and nitric oxide (NO), further contributing to oxidative stress and neuronal injury (Morgan et al., 2005; Famenini et al., 2017; Munawara et al., 2021; Fiala et al., 2005).

The interplay between these two cells represents a double-edged sword in AD pathology. While coordinated activity between them may serve protective functions in the initial stages, chronic dysregulation of their communication could drive neuroinflammatory processes that lead to synaptic dysfunction and neuronal death (Morgan et al., 2005; Zhao et al., 2020; Famenini et al., 2017; Munawara et al., 2021; Fiala et al., 2005; Fani Maleki and Rivest, 2019; Medd, 2025; Naert and Rivest, 2013). Understanding how to modulate the crosstalk between MDMs and microglia offers potential therapeutic avenues for dampening harmful inflammation and slowing neurodegeneration in AD.

Beyond their interaction with microglia, MDMs also engage with other brain-resident cells that influence the inflammatory landscape of AD. MDM-associated cytokines can activate astrocytes, contributing to gliosis and promoting secondary inflammatory cascades (Martin et al., 2017; Krabbe et al., 2013; Podleśny-Drabiniok et al., 2025). Moreover, MDMs can directly affect neuronal function through the production of reactive species and inflammatory mediators, which may disrupt synaptic signaling and viability (Krabbe et al., 2013; Zhao et al., 2020; Michaud et al., 2013). Interactions with other infiltrating immune cells, such as neutrophils, further complicate this immune environment; neutrophil infiltration via LFA-1 has been shown to exacerbate cognitive decline in AD models (Villacampa and Heneka, 2020; Zenaro et al., 2015; Silvin et al., 2022). Understanding the interplays of MDM with other resident and infiltrating cells in the CNS environment will provide valuable information for the development of AD therapies.

3. Conclusion

As innate immune cells of the myeloid lineage residing in the CNS, microglia were once believed to have been derived from bone marrow and later migrate to the CNS in a similar way in which tissue-specific macrophages translocate. These assumptions were based on the similarities in morphology and cell surface markers that exist between microglia and monocellular phagocytes. Since these assumptions, it is now established that microglial progenitors arise from progenitors in the embryonic yolk sac that seed the brain and appear to mature there. Mechanistically, microglia migrating to the brain after development mirrors the development of monocyte-derived macrophages in the brain. This raises the notion that circulating monocytes may contribute to AD pathology, in which locality has driven the previous literature toward local cell types, yet proximal cells may be key players in all stages of the disease progression. The dual roles of MDMs in AD underscore their importance as both potential allies and contributors to disease pathology. While MDMs can assist in Aβ clearance, their involvement in chronic neuroinflammation may accelerate neuronal degeneration. This complex functionality offers a compelling case for therapeutic interventions targeting MDM recruitment and polarization. By modulating their role in AD, future therapies may harness MDMs’ beneficial effects while mitigating their pro-inflammatory actions, potentially leading to novel treatment strategies for AD. Therefore, studying MDMs in AD will strengthen our understanding of microglia: macrophage relationships, communication, pathways, as well as deepen our comprehension of monocytes not only within the immune system, but beyond.

Data availability

No data was used for the research described in the article.