ArticleImmunity & ageing : I & A2021
Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease.
Article in Immunity & ageing : I & A, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- A systematic review and meta-analysis of pteridines in mild cognitive impairment and Alzheimer's disease.BMC geriatrics · 2025Pooled it
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- The Relationship between Biological Aging and Cognitive Function: A Machine Learning Model.Yonsei medical journal · 2026Article
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- Immune cell subsets linking insomnia trajectories and incident cognitive impairment: a prospective cohort study.BMC medicine · 2026Article
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- Early peripheral immune signaling precedes tau elevation and blood-brain barrier disruption in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- The spleen-brain axis in Alzheimer's disease and related dementias: Integrating immune and metabolic regulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Immune dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2026Review
- Emerging pathological mechanisms of Alzheimer's disease pathogenesis: from neuroimmune interactions to intercellular communication.Frontiers in aging neuroscience · 2026Review
- Peripheral immune profiling in frontotemporal dementia.Brain communications · 2026Article
- Monocyte inflammation and resilience to Alzheimer's disease: novel genetic risk genes identified by transcriptome-wide association study.Translational psychiatry · 2025Article
- The immune response within Alzheimer's disease: from the lense of peripheral monocyte-derived macrophages.Journal of neuroimmunology · 2025Review
- Understanding monocyte-driven neuroinflammation in Alzheimer's disease using human cortical organoid microphysiological systems.Science advances · 2025Article
- Adaptive Immune Dyshomeostasis as a Mediator of Vascular Cognitive Decline: Unraveling Neurovascular Crosstalk.Aging and disease · 2025Review
- Immune cells in Alzheimer's disease: insights into pathogenesis and potential therapeutic targets.Medical review (2021) · 2025Review
- Elucidating the role of peripheral monocyte nicotinic acetylcholine receptors and inflammation in cognitive outcomes in older adults.Biogerontology · 2025Article
- Amyloid-β and heart failure in Alzheimer's disease: the new vistas.Frontiers in medicine · 2025Review
- Anti-Neuroinflammatory Effects of a Novel Bile Acid Derivative.International journal of molecular sciences · 2024Article
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Authors and funding
21 authors at 9 institutions in 9 countries.
Funding
Abstract
backgroundAlzheimer's disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of peripheral monocytes/macrophages is still largely unknown, especially concerning their role in the various stages of AD.
objectivesAD develops over decades and its clinical manifestation is preceded by subjective memory complaints (SMC) and mild cognitive impairment (MCI); thus, the question arises how the peripheral innate immune response changes with the progression of the disease. Therefore, to further investigate the roles of monocytes/macrophages in the progression of AD we assessed their phenotypes and functions in patients at SMC, MCI and AD stages and compared them with cognitively healthy controls. We also conceptualised an idealised mathematical model to explain the functionality of monocytes/macrophages along the progression of the disease.
resultsWe show that there are distinct phenotypic and functional changes in monocyte and macrophage populations as the disease progresses. Higher free radical production upon stimulation could already be observed for the monocytes of SMC patients. The most striking results show that activation of peripheral monocytes (hyperactivation) is the strongest in the MCI group, at the prodromal stage of the disease. Monocytes exhibit significantly increased chemotaxis, free radical production, and cytokine production in response to TLR2 and TLR4 stimulation.
conclusionOur data suggest that the peripheral innate immune system is activated during the progression from SMC through MCI to AD, with the highest levels of activation being in MCI subjects and the lowest in AD patients. Some of these parameters may be used as biomarkers, but more holistic immune studies are needed to find the best period of the disease for clinical intervention.
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