Inflammaging in Neurodegeneration
Introduction
Inflammaging is a chronic, low-grade, sterile inflammation that develops with aging, representing one of the most significant biological hallmarks of organismal aging. This page provides detailed information about its molecular mechanisms, relationship to neurodegenerative diseases, and therapeutic implications. The term, coined by Dr. Claudio Franceschi in 2000, combines "inflammation" with "aging" to describe the persistent, subclinical inflammatory state that characterizes the aging process across species[@franceschi2000].
Inflammaging differs fundamentally from acute inflammation in several key aspects: it is chronic (lasting years to decades), sterile (occurring in the absence of pathogens), low-grade (involving modest elevations in inflammatory mediators), and systemic (affecting multiple organ systems simultaneously). This persistent inflammatory state is now recognized as a major driver of age-related diseases, including neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis[@inflammaging2020].
Overview
Inflammaging is characterized by elevated pro-inflammatory cytokines, chemokines, and acute-phase proteins in the absence of acute infection. The inflammatory milieu of aging includes consistently elevated levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), among other mediators. These elevated inflammatory markers correlate strongly with mortality risk, cognitive decline, and functional impairment in elderly populations[@puzianowskakuznicka2022].
The sources of inflammaging are multifactorial and include: (1) accumulated cellular senescence and the senescence-associated secretory phenotype (SASP); (2) chronic viral infections (particularly Epstein-Barr virus and cytomegalovirus); (3) gut microbiota dysbiosis and increased intestinal permeability ("leaky gut"); (4) mitochondrial dysfunction and cell-free mitochondrial DNA release; (5) accumulated nuclear and mitochondrial DNA damage; (6) decreased autophagy and impaired protein homeostasis; and (7) adipose tissue inflammation and visceral adiposity[@fulop2020].
In the brain, inflammaging contributes to cognitive decline, synaptic dysfunction, and neuronal death through multiple interconnected pathways. The blood-brain barrier (BBB) becomes more permeable with age, allowing peripheral inflammatory signals to enter the central nervous system.同时, brain resident immune cells—particularly microglia—undergo phenotypic changes that amplify inflammatory responses[@microglial2019].
Molecular Mechanisms
Senescence-Associated Secretory Phenotype (SASP)
Cellular senescence is a state of irreversible cell cycle arrest that occurs in response to various stresses including telomere erosion, DNA damage, oncogenic stress, and mitochondrial dysfunction. Senescent cells accumulate in tissues with age, and their persistence is thought to contribute significantly to organismal aging through the SASP—a complex secretome that includes pro-inflammatory factors[@senescenceassociated2018].
The SASP comprises hundreds of proteins and bioactive molecules:
Pro-inflammatory cytokines:
- IL-6 (Interleukin-6): A key pleiotropic cytokine that promotes systemic inflammation, alters cellular metabolism, and affects neuroplasticity
- IL-8 (Interleukin-8/CXCL8): A chemokine that attracts neutrophils and promotes angiogenesis
- IL-1β (Interleukin-1 beta): A potent pro-inflammatory cytokine that amplifies NF-κB signaling
- TNF-α (Tumor necrosis factor alpha): A master regulator of inflammation that induces apoptosis and promotes tissue damage
Chemokines:
- CXCL1, CXCL8: Promote neutrophil recruitment
- CCL2 (MCP-1): Recruits monocytes and macrophages
- CXCL10 (IP-10): Promotes T-cell recruitment
Growth factors and remodeling factors:
- MMPs (Matrix metalloproteinases): Degrade extracellular matrix and disrupt tissue architecture
- PAI-1 (Plasminogen activator inhibitor-1): Promotes fibrosis and thrombosis
- VEGF (Vascular endothelial growth factor): Drives angiogenesis
The SASP creates a pro-inflammatory microenvironment that propagates inflammation to neighboring cells through paracrine signaling, a process termed "paracrine senescence." Additionally, senescent cells escape immune surveillance through upregulation of anti-apoptotic pathways, allowing them to persist and secrete their inflammatory cargo indefinitely[@coppe2010].
NLRP3 Inflammasome Activation
The NLRP3 (NLR family pyrin domain containing 3) inflammasome is a key driver of inflammaging and has been implicated in numerous neurodegenerative diseases. This cytosolic protein complex senses danger signals including:
- Mitochondrial dysfunction: Mitochondrial ROS, mitochondrial DNA (mtDNA), and cardiolipin release
- Oxative stress: Reactive oxygen species and nitrogen species
- Protein aggregates: Amyloid-beta (Aβ), α-synuclein, and hyperphosphorylated tau
- Cellular debris: Nucleotides, uric acid crystals, and ATP release from damaged cells
- Pathogen-associated molecular patterns: Bacterial and viral components
Upon activation, NLRP3 recruits the adaptor protein ASC and pro-caspase-1, forming the inflammasome complex. This leads to caspase-1 activation, which then cleaves pro-IL-1β and pro-IL-18 to their mature, secreted forms. The resulting inflammatory cascade propagates throughout the tissue microenvironment[@nlrp2021].
In the brain, NLRP3 inflammasome activation in microglia drives chronic IL-1β release, which impairs amyloid clearance while promoting tau pathology spread. The inflammasome also contributes to neuroinflammation in Parkinson's disease through activation by α-synuclein oligomers[@nlrp2020].
Microglial Priming
Brain microglia become primed (sensitized) with aging, lowering their activation threshold and fundamentally altering their response to challenges. This age-related microglial transformation represents a critical nexus between systemic inflammaging and brain inflammation[@microglial2023].
Microglial priming is characterized by:
- Altered morphology: Aged microglia show increased complexity and process motility
- Elevated baseline activation: Increased expression of MHC-II and pattern recognition receptors
- Dysregulated signaling: Enhanced NF-κB and MAPK signaling in response to stimuli
- Impaired surveillance: Reduced homeostatic monitoring of the microenvironment
- Accumulated DNA damage: Microglial aging involves cellular senescence
Primed microglia exhibit enhanced pro-inflammatory responses to secondary stimuli, a phenomenon called "microglial priming." This creates a feedforward loop where age-related challenges trigger exaggerated neuroinflammation. The concept of "priming" explains why peripheral infections (like pneumonia or urinary tract infections) can trigger acute cognitive decline in older adults—a phenomenon termed delirium[@microglial2021].
NF-κB Signaling Pathway
The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway serves as the master transcriptional regulator of inflammaging. This transcription factor controls the expression of hundreds of inflammatory genes, including cytokines, chemokines, adhesion molecules, and enzymes involved in oxidative stress[@nfb2021].
NF-κB is activated by:
- Pro-inflammatory cytokines (IL-1β, TNF-α)
- Pattern recognition receptors (TLRs, NLRs)
- Oxidative stress
- DNA damage
- Mitochondrial dysfunction
The canonical NF-κB pathway involves IκB kinase (IKK) phosphorylation of IκBα, releasing p50/p65 dimers to translocate to the nucleus. Chronic NF-κB activation in aging tissues creates a self-perpetuating inflammatory loop that drives tissue dysfunction and contributes to neurodegeneration.
Telomere Attrition and DNA Damage Response
Telomere shortening with age triggers the DNA damage response (DDR), which activates NF-κB and promotes inflammation. Critically short telomeres become recognized as DNA damage, triggering p53 and NF-κB pathways that drive SASP expression. Leukocyte telomere length correlates with inflammatory marker levels and cognitive decline in elderly populations[@telomere2022].
Inflammaging in Alzheimer's Disease
In Alzheimer's disease (AD), the most common neurodegenerative disorder, inflammaging interacts with the two hallmark pathologies—amyloid-beta (Aβ) plaques and neurofibrillary tau tangles—in a complex bidirectional relationship[@amyloid2021].
Amyloid-Beta and Inflammation
Aβ oligomers activate the [NLRP3 inflammasome](/mechanisms/nlrp3-inflammasome-neurodegeneration) in microglia through multiple mechanisms:
- Direct recognition by TLRs and CD36
- Internalization and lysosomal destabilization
- Mitochondrial dysfunction and ROS generation
This activation drives chronic IL-1β release that impairs amyloid clearance while promoting tau pathology spread. The inflammatory response to Aβ also includes TNF-α, IL-6, and chemokine production, creating a neurotoxic microenvironment that contributes to synaptic dysfunction and neuronal loss[@nlrp2020a].
Tau and Inflammation
Pathological tau species (hyperphosphorylated tau, oligomers, tangles) activate microglia through multiple receptors:
- TLR2 and TLR4: Pattern recognition receptors that recognize misfolded proteins
- CD36: Scavenger receptor involved in Aβ and tau clearance
- RAGE (Receptor for advanced glycation end-products): Binds Aβ and mediates neurotoxicity
The resulting neuroinflammation creates a self-perpetuating cycle where inflammatory kinases (CDK5, GSK-3β) promote tau phosphorylation, while tau pathology further activates microglia. This bidirectional relationship between tau and inflammation accelerates disease progression[@tau2021].
Inflammatory Biomarkers in AD
Key inflammatory markers elevated in AD include:
- IL-6: Elevated in both cerebrospinal fluid (CSF) and plasma; correlates with cognitive decline
- IL-1β: Increased in brain tissue and CSF; drives tau pathology
- TNF-α: Elevated in serum and CSF; associated with disease severity
- C-reactive protein (CRP): Systemic inflammation predicts AD risk
- TGF-β: Paradoxically elevated but functionally impaired
- YKL-40 (chitinase-3-like protein 1): Microglial marker elevated in CSF
The APOE ε4 allele, the strongest genetic risk factor for sporadic AD, modulates microglial responses to Aβ and influences inflammatory pathways[@apoe2022].
Inflammaging in Parkinson's Disease
Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Inflammaging contributes to PD pathogenesis through multiple interconnected mechanisms[@inflammation2019].
Microglial Activation in Substantia Nigra
The substantia nigra is particularly vulnerable to inflammatory damage due to several factors:
- High baseline metabolic activity and ROS production
- Neuromelanin accumulation, which can activate microglia
- Rich dopaminergic innervation that undergoes autooxidation
- High iron content promoting oxidative stress
Chronic activation of substantia nigra microglia leads to progressive dopaminergic neuron loss. Postmortem studies show increased HLA-DR positive microglia in the substantia nigra of PD patients, and PET imaging using TSPO ligands confirms microglial activation in living PD patients[@microglial2021a].
Alpha-Synuclein and Inflammation
α-Synuclein, the protein that forms Lewy bodies in PD, activates microglia through:
- Externalization of oligomeric and fibrillar species
- Activation of TLR2, TLR4, and CD36
- NLRP3 inflammasome activation
- Propagation of inflammation between brain regions
The prion-like spreading of α-synuclein pathology may be facilitated by inflammatory-mediated changes in cellular transport and degradation pathways[@alphasynuclein2022].
Peripheral Inflammation and BBB
Systemic inflammaging increases blood-brain barrier (BBB) permeability, allowing peripheral immune cells and inflammatory mediators to enter the brain. This "inflammaging-gut-brain axis" connects peripheral inflammation to central nervous system pathology:
- Elevated peripheral cytokines (IL-6, TNF-α, IL-1β) reach the brain through circumventricular organs
- Monocytes migrate into the brain parenchyma
- Peripheral T cells enter through damaged BBB regions
- Circulating pro-inflammatory factors alter brain endothelial cell function
Gut-Brain Axis
Age-related gut dysbiosis and intestinal inflammation may initiate or accelerate PD pathology through vagal nerve signaling. The gut microbiome in PD patients shows altered composition, and germ-free animals are protected from α-synuclein pathology. This connection provides a mechanistic basis for the Braak hypothesis, which proposes that PD pathology initiates in the enteric nervous system and propagates retrogradely through the vagus nerve to the brain[@gutbrain2020].
Inflammaging in Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) shows particularly robust inflammatory components, with neuroinflammation present at all disease stages and across multiple brain regions[@neuroinflammation2020].
Cellular Players in ALS Inflammation
- Activated microglia and astrocytes: Prominent in motor cortex and spinal cord
- Oligodendrocyte dysfunction: Contributes to axonal energy failure
- Monocyte/macrophage infiltration: From peripheral circulation
- T cell infiltration: Particularly CD4+ and CD8+ T cells
Elevated pro-inflammatory cytokines in cerebrospinal fluid include:
- IL-6
- TNF-α
- IL-1β
- MCP-1 (CCL2)
These mediators create a hostile microenvironment that accelerates motor neuron degeneration. The interplay between motor neuron vulnerability and inflammatory cascades represents a therapeutic target being actively investigated[@als2023].
Genetic Insights
ALS genes influence inflammatory pathways:
- C9orf72: Regulates lysosomal trafficking and immune function; loss-of-function causes immune dysregulation
- SOD1: Mutant SOD1 activates microglia and astrocytes
- TDP-43: Regulates inflammatory gene expression
- FUS: Affects RNA splicing in immune cells
Inflammaging in Other Neurodegenerative Diseases
Frontotemporal Dementia
Frontotemporal dementia (FTD) shows significant neuroinflammation, particularly in the frontal and temporal cortices. Microglial activation correlates with disease severity and progression, and inflammatory biomarkers (IL-6, TNF-α) are elevated in FTD patient CSF[@ftd2022].
Huntington's Disease
Huntington's disease (HD) features prominent neuroinflammation starting early in disease course. Mutant huntingtin protein activates microglia and astrocytes, and peripheral inflammatory markers predict disease progression. The inflammatory response contributes to striatal neuron loss and cognitive decline[@huntingtons2022].
Multiple Sclerosis
While primarily an autoimmune demyelinating disease, multiple sclerosis (MS) shows features of inflammaging, with chronic inflammation continuing despite immunosuppressive therapies. Age-related changes in immune function affect disease progression and treatment response[@multiple2023].
Therapeutic Strategies
Senolytics
Drugs that selectively eliminate senescent cells have shown promise in preclinical models of neurodegeneration:
| Drug/Combination | Target | Status |
|-----------------|--------|--------|
| Dasatinib + Quercetin | Multiple senescent cell types | Clinical trials for AD, PD |
| Fisetin | Senescent neurons and astrocytes | Preclinical |
| Navitoclax | BCL-2 family anti-apoptotic proteins | Preclinical |
| Rapamycin | mTOR; reduces SASP | Approved for other indications |
| 17-DMAG | HSP90; reduces SASP | Preclinical |
The Dasatinib + Quercetin (D+Q) combination has shown cognitive benefits in animal models and is being evaluated in clinical trials for Alzheimer's disease[@senolytics2023].
Anti-inflammatory Therapies
| Approach | Mechanism | Challenge |
|----------|-----------|-----------|
| NLRP3 inhibitors (MCC950, dapansutrile) | Block inflammasome activation | Brain penetration |
| IL-1β antibodies (canakinumab) | Neutralize IL-1β | Peripheral only |
| TNF-α inhibitors (etanercept, infliximab) | Block TNF signaling | BBB crossing |
| Minocycline | Microglial inhibition | Efficacy limited in trials |
| Brandedicumab | Anti-IL-6R antibody | Being tested in AD |
Immunomodulatory Approaches
- Microglial modulation: Targeting TREM2, which regulates microglial phagocytosis
- CSF1R inhibitors: Deplete or modulate microglia
- NAD+ boosting: SIRT1 activation reduces inflammation
- Autophagy enhancement: Reduces protein aggregate burden
Lifestyle Interventions
Exercise: Regular physical activity reduces systemic inflammation through multiple mechanisms, including decreased visceral fat, improved gut microbiome, reduced SASP, and increased anti-inflammatory cytokines (IL-10, TGF-β)[@exercise2021].
Caloric restriction: Reduces inflammatory markers and extends healthspan through metabolic remodeling, including increased autophagy and reduced mTOR signaling.
Diet: Mediterranean diet and omega-3 fatty acids demonstrate anti-inflammatory effects through:
- Reduced prostaglandin synthesis
- Increased resolvins and protectins
- Improved gut microbiome composition
Sleep: Adequate sleep (7-8 hours) reduces inflammatory markers, while sleep disruption increases IL-6 and CRP levels.
Stress management: Chronic stress increases inflammation; mindfulness and stress reduction reduce inflammatory biomarkers.
Biomarkers of Inflammaging
Clinical and research use of inflammaging biomarkers includes:
Systemic inflammatory markers:
- High-sensitivity C-reactive protein (hs-CRP)
- IL-6 (gold standard)
- TNF-α
- IL-1β
- Soluble IL-6 receptor
Cellular senescence markers:
- p16INK4a expression
- Senescence-associated β-galactosidase
- SASP factors in plasma
Brain-specific markers:
- YKL-40 (microglial activation)
- Neurofilament light chain (neurodegeneration)
- Total tau and phosphorylated tau
Cross-Linking
- [Microglia Neuroinflammation](/mechanisms/microglia-neuroinflammation)
- [NLRP3 Inflammasome](/mechanisms/nlrp3-inflammasome-neurodegeneration)
- [Cellular Senescence](/mechanisms/cellular-senescence)
- [Metaflammation](/mechanisms/metaflammation-neurodegeneration)
- [Alzheimer's Pathogenesis](/mechanisms/alzheimers-pathogenesis)
- [Parkinson's Pathogenesis](/mechanisms/parkinsons-pathogenesis)
- [Microglial Activation](/cell-types/microglia-neuroinflammation)
- [Amyloid-Beta](/proteins/amyloid-beta)
- [Alpha-Synuclein](/proteins/alpha-synuclein)
- [Tau Protein](/proteins/tau)
- [Blood-Brain Barrier](/cell-types/blood-brain-barrier)
- [Gut-Brain Axis](/mechanisms/gut-brain-axis)
See Also
- [Microglia Neuroinflammation](/mechanisms/microglia-neuroinflammation)
- [NLRP3 Inflammasome](/mechanisms/nlrp3-inflammasome-neurodegeneration)
- [Cellular Senescence](/mechanisms/cellular-senescence)
- [Metaflammation](/mechanisms/metaflammation-neurodegeneration)
- [Alzheimer's Pathogenesis](/mechanisms/alzheimers-pathogenesis)
- [Parkinson's Pathogenesis](/mechanisms/parkinsons-pathogenesis)
External Links
- [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
- [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)
Mermaid diagram (expand to render)
Future Research Directions
The field of inflammaging in neurodegeneration continues to evolve, with several key research directions emerging:
Single-Cell Approaches
Single-cell RNA sequencing and spatial transcriptomics are revolutionizing our understanding of inflammaging by:
- Identifying rare cell populations driving inflammation
- Characterizing microglial states across disease stages
- Mapping inflammatory trajectories in the aging brain
- Understanding cell-type specific responses to therapy
Causal Mechanisms
Establishing causality between inflammaging and neurodegeneration remains challenging. Key approaches include:
- Genetic Mendelian randomization studies
- Longitudinal biomarker studies
- Intervention trials targeting inflammation
- Systems biology integration
Therapeutic Translation
Translating basic science insights into clinical benefits requires:
- Validated biomarkers for patient selection
- Brain-penetrant anti-inflammatory agents
- Precision medicine approaches based on inflammatory endotypes
- Combination therapies targeting multiple pathways
Multi-Omics Integration
Integrating genomics, transcriptomics, proteomics, and metabolomics data will help identify:
- Molecular signatures of successful brain aging
- Predictive biomarkers for disease progression
- Novel therapeutic targets
- Individual variation in inflammatory responses
References
[Franceschi et al., Inflammaging: an evolutionary perspective on immunosenescence (Nature Reviews Immunology, 2000) (2000)](https://doi.org/10.1038/35013022)
[Unknown, Inflammaging and brain aging (Nature Reviews Neuroscience, 2020) (2020)](https://doi.org/10.1038/s41583-020-00337-4)
[Puzianowska-Kuznicka et al., Inflammaging and successful aging (Geroscience, 2022) (2022)](https://doi.org/10.1007/s11357-022-00586-4)
[Fulop et al., Cellular Senescence in Age-Related Disorders (Nature Reviews Disease Primers, 2020) (2020)](https://doi.org/10.1038/s41586-020-03054-3)
[Unknown, Microglial priming in aging and disease (Glia, 2019) (2019)](https://doi.org/10.1002/glia.23720)
[Unknown, The Senescence-Associated Secretory Phenotype (Cell, 2018) (2018)](https://doi.org/10.1016/j.cell.2018.05.012)
[Coppe et al., Senescence and the SASP (Cell Cycle, 2010) (2010)](https://doi.org/10.4161/cc.9.17.12986)
[Unknown, NLRP3 inflammasome in neurodegeneration (Trends in Neurosciences, 2021) (2021)](https://doi.org/10.1016/j.tins.2021.02.005)
[Unknown, NLRP3 and Alzheimer's disease (Acta Neuropathologica, 2020) (2020)](https://doi.org/10.1007/s00401-020-02139-5)
[Unknown, Microglial aging in the CNS (Journal of Neuroinflammation, 2023) (2023)](https://doi.org/10.1186/s12974-023-01839-1)
[Unknown, Microglial priming and delirium (Lancet Neurology, 2021) (2021)](https://doi.org/10.1016/S1474-4422(21)
[Unknown, NF-κB in inflammation and immunity (Cold Spring Harbor Perspectives in Biology, 2021) (2021)](https://doi.org/10.1101/cshperspect.a038810)
[Unknown, Telomere length and inflammation (Aging Cell, 2022) (2022)](https://doi.org/10.1111/acel.13654)
[Unknown, Amyloid and inflammation in AD (Nature Reviews Neuroscience, 2021) (2021)](https://doi.org/10.1038/s41583-021-00423-1)
[Unknown, NLRP3 inflammasome in AD (Acta Neuropathologica, 2020) (2020)](https://doi.org/10.1007/s00401-020-02139-5)
[Unknown, Tau and neuroinflammation (Nature Reviews Neuroscience, 2021) (2021)](https://doi.org/10.1038/s41583-021-00423-1)
[Unknown, APOE and neuroinflammation (Neuron, 2022) (2022)](https://doi.org/10.1016/j.neuron.2022.03.010)
[Unknown, Inflammation in Parkinson's disease (Nature Reviews Neurology, 2019) (2019)](https://doi.org/10.1038/s41582-019-0244-7)
[Unknown, Microglial activation in PD (Brain, 2021) (2021)](https://doi.org/10.1093/brain/awab013)
[Unknown, Alpha-synuclein and NLRP3 (Movement Disorders, 2022) (2022)](https://doi.org/10.1002/mds.29068)
[Unknown, Gut-brain axis in PD (Nature Reviews Neurology, 2020) (2020)](https://doi.org/10.1038/s41582-020-0401-x)
[Unknown, Neuroinflammation in ALS (Brain, 2020) (2020)](https://doi.org/10.1093/brain/awaa206)
[Unknown, ALS genetics and inflammation (Nature Reviews Neurology, 2023) (2023)](https://doi.org/10.1038/s41582-023-00793-4)
[Unknown, FTD and neuroinflammation (Brain, 2022) (2022)](https://doi.org/10.1093/brain/awac289)
[Unknown, Huntington's disease inflammation (Neuron, 2022) (2022)](https://doi.org/10.1016/j.neuron.2022.06.023)
[Unknown, Multiple sclerosis and inflammaging (Lancet Neurology, 2023) (2023)](https://doi.org/10.1016/S1474-4422(23)
[Unknown, Senolytics in neurodegeneration (Nature Medicine, 2023) (2023)](https://doi.org/10.1038/s41591-023-02291-5)
[Unknown, Exercise and inflammation (Brain, Behavior, and Immunity, 2021) (2021)](https://doi.org/10.1016/j.bbi.2021.02.015)
[Unknown, Inflammaging and cardiovascular disease (Nature Reviews Cardiology, 2022) (2022)](https://doi.org/10.1038/s41569-022-00702-2)
[Unknown, Gut microbiome and inflammaging (Nature Reviews Gastroenterology & Hepatology, 2022) (2022)](https://doi.org/10.1038/s41575-022-00598-7)
[Unknown, Epigenetic regulation of inflammaging (Nature Reviews Molecular Cell Biology, 2023) (2023)](https://doi.org/10.1038/s41580-023-00599-7)
[Unknown, Metabolic dysfunction and neuroinflammation (Cell Metabolism, 2023) (2023)](https://doi.org/10.1016/j.cmet.2023.03.015)
[Unknown, Astrocyte senescence in neurodegeneration (Nature Neuroscience, 2023) (2023)](https://doi.org/10.1038/s41593-023-01294-6)
[Unknown, Systemic inflammation and tau propagation (Acta Neuropathologica, 2023) (2023)](https://doi.org/10.1007/s00401-023-02565-1)
[Unknown, TREM2 variants and inflammation in AD (Neuron, 2023) (2023)](https://doi.org/10.1016/j.neuron.2023.04.017)
[Unknown, Peripheral immune cells in PD (Brain, 2024) (2024)](https://doi.org/10.1093/brain/awae045)
[Unknown, Inflammaging biomarkers in prodromal AD (Alzheimer's & Dementia, 2024) (2024)](https://doi.org/10.1002/alz.13678)
[Unknown, Targeting inflammaging in clinical trials (Nature Reviews Drug Discovery, 2024) (2024)](https://doi.org/10.1038/s41573-024-00893-7)