Neuroinflammation in Alzheimer and Parkinson Disease

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Neuroinflammation in Alzheimer's and Parkinson's Disease

Overview

Neuroinflammation is a fundamental pathological hallmark of neurodegenerative diseases, characterized by chronic activation of glial cells (microglia and astrocytes) and sustained elevation of pro-inflammatory mediators in the central nervous system. While acute neuroinflammation serves as a protective response to injury or infection, the transition to chronic neuroinflammation becomes maladaptive and contributes significantly to neuronal death, synaptic loss, and disease progression in both Alzheimer's disease (AD) and Parkinson's disease (PD)[@heneka2015][heneka2015 2015, heneka2015](https://pubmed.ncbi.nlm.nih.gov/29439059/)[glass2010 2010, glass2010](https://pubmed.ncbi.nlm.nih.gov/20421449/).

The past decade has witnessed a paradigm shift in our understanding of neuroinflammation, moving from the view of it as a secondary phenomenon to recognition of its central role in disease initiation and propagation. Microglia, the resident immune cells of the brain, have emerged as critical players in neurodegeneration, with genome-wide association studies (GWAS) identifying multiple microglial genes as risk factors for AD and PD[@deczkowska2021][deczkowska2021 2021, deczkowska2021](https://pubmed.ncbi.nlm.nih.gov/34758333/).

Introduction

...

Neuroinflammation in Alzheimer's and Parkinson's Disease

Overview

Neuroinflammation is a fundamental pathological hallmark of neurodegenerative diseases, characterized by chronic activation of glial cells (microglia and astrocytes) and sustained elevation of pro-inflammatory mediators in the central nervous system. While acute neuroinflammation serves as a protective response to injury or infection, the transition to chronic neuroinflammation becomes maladaptive and contributes significantly to neuronal death, synaptic loss, and disease progression in both Alzheimer's disease (AD) and Parkinson's disease (PD)[@heneka2015][heneka2015 2015, heneka2015](https://pubmed.ncbi.nlm.nih.gov/29439059/)[glass2010 2010, glass2010](https://pubmed.ncbi.nlm.nih.gov/20421449/).

The past decade has witnessed a paradigm shift in our understanding of neuroinflammation, moving from the view of it as a secondary phenomenon to recognition of its central role in disease initiation and propagation. Microglia, the resident immune cells of the brain, have emerged as critical players in neurodegeneration, with genome-wide association studies (GWAS) identifying multiple microglial genes as risk factors for AD and PD[@deczkowska2021][deczkowska2021 2021, deczkowska2021](https://pubmed.ncbi.nlm.nih.gov/34758333/).

Introduction

Neuroinflammation encompasses a complex cascade of cellular and molecular events involving the activation of microglia, astrocytes, endothelial cells, and peripheral immune cells. This inflammatory response is mediated by a network of cytokines, chemokines, reactive oxygen species (ROS), and signaling pathways that, when dysregulated, create a neurotoxic environment[glass2010 2010, glass2010](https://pubmed.ncbi.nlm.nih.gov/20421449/).

In Alzheimer's disease, neuroinflammation is intimately linked to the two core pathological hallmarks: amyloid-beta (Aβ) plaques and tau neurofibrillary tangles. Microglial cells cluster around amyloid plaques in characteristic patterns, and evidence suggests that chronic microglial activation may precede detectable amyloid deposition in some cases[lambert2013 2013, lambert2013](https://pubmed.ncbi.nlm.nih.gov/24162737/). Similarly, in Parkinson's disease, neuroinflammation accompanies alpha-synuclein aggregation and dopaminergic neuron loss in the substantia nigra pars compacta (SNc), with post-mortem studies consistently demonstrating elevated inflammatory markers in affected brain regions[hirsch2009 2009, Neuroinflammation in Parkinson](https://pubmed.ncbi.nlm.nih.gov/19368151/).

Key Inflammatory Mediators

Cytokines

Cytokines are small signaling proteins that mediate cell-to-cell communication during inflammation. In neurodegeneration, pro-inflammatory cytokines create a self-perpetuating cycle of glial activation and neuronal damage[heneka2015 2015, heneka2015](https://pubmed.ncbi.nlm.nih.gov/29439059/)[cunningham2013 2013, cunningham2013](https://pubmed.ncbi.nlm.nih.gov/24065048/).

| Cytokine | Primary Source | Role in Neurodegeneration | Clinical Relevance |
|----------|---------------|--------------------------|-------------------|
| IL-1β | Microglia, astrocytes | Promotes tau phosphorylation and aggregation; induces synaptic dysfunction; enhances Aβ production | Elevated in AD and PD CSF; associated with disease severity |
| IL-6 | Glial cells, neurons | Neurotoxic effects; impairs adult neurogenesis; disrupts synaptic plasticity | Serum IL-6 predicts cognitive decline in AD |
| TNF-α | Microglia, astrocytes | Induces neuronal apoptosis; disrupts blood-brain barrier (BBB); amplifies neuroinflammation | Anti-TNF therapies in clinical trials for AD/PD |
| IL-18 | Microglia | Pro-inflammatory; activates caspase-1 and the NLRP3 inflammasome; promotes tau pathology[@maphis2015] | Elevated in AD and PD brains[maphis2015 2015, maphis2015](https://pubmed.ncbi.nlm.nih.gov/25888545/) |
| IFN-γ | T cells, NK cells | Promotes microglial activation; contributes to synaptic loss | Associated with faster disease progression |

Chemokines

Chemokines are small cytokines that direct immune cell migration and positioning. They play crucial roles in recruiting peripheral immune cells to the brain and regulating microglial surveillance behavior[ransohoff2014 2014, Chemokines and chemokine receptors: standing at the crossroads of immunobiolo...](https://pubmed.ncbi.nlm.nih.gov/25308688/).

CCL2 (MCP-1): Chemoattractant for monocytes and microglia; elevated in AD and PD brains; promotes neuroinflammation
CXCL12 (SDF-1): Regulates microglial migration and process motility; implicated in Aβ-induced neurotoxicity
CX3CL1 (Fractalkine): Membrane-bound and soluble forms mediate neuron-microglia communication; CX3CR1 deficiency enhances neuroinflammation in mouse models
CXCL10 (IP-10): Induced by IFN-γ; elevated in AD and PD brains; attracts T cells to the CNS
CCL5 (RANTES): Pro-inflammatory chemokine; elevated in AD and PD cerebrospinal fluid (CSF)

Signaling Pathways

Multiple signaling pathways coordinate the neuroinflammatory response and represent attractive therapeutic targets[liu2017 2017, liu2017](https://pubmed.ncbi.nlm.nih.gov/28648371/).

NF-κB pathway: Master regulator of inflammatory gene expression; activated by Aβ, tau, and alpha-synuclein; induces transcription of cytokines, chemokines, and adhesion molecules

MAPK pathways: p38, JNK, and ERK signaling mediate stress-induced inflammation; p38 inhibitors in clinical development

JAK-STAT pathway: Cytokine signaling cascade; STAT1 and STAT3 activation in glia; associated with neurotoxic phenotype

NLRP3 inflammasome: Cytoplasmic complex that activates caspase-1 and processes pro-IL-1β and pro-IL-18; activated by Aβ and alpha-synuclein; genetic variants increase AD risk

TREM2 signaling: Triggering receptor expressed on myeloid cells 2; regulates microglial phagocytosis, survival, and inflammatory response; AD risk variants impair microglial function

Molecular Mechanisms in Alzheimer's Disease

Microglial Activation States

Microglia exist in a spectrum of activation states, transitioning from homeostatic surveillance to disease-associated phenotypes. Single-cell RNA sequencing has revealed remarkable heterogeneity in microglial states across brain regions and disease stages[deczkowska2021 2021, deczkowska2021](https://pubmed.ncbi.nlm.nih.gov/34758333/)[kerenshaul2017 2017, kerenshaul2017](https://pubmed.ncbi.nlm.nih.gov/28593980/).

Homeostatic microglia survey the brain parenchyma, extending and retracting processes every few minutes. They express low levels of inflammatory genes and high levels of genes involved in phagocytosis (e.g., TREM2, CD33).

Disease-associated microglia (DAM) upregulate a distinct gene program including APOE, TREM2, and genes involved in lipid metabolism. DAM cluster around amyloid plaques in a TREM2-dependent manner and may play both protective (Aβ clearance) and harmful (pro-inflammatory) roles.

Neurodegenerative microglia (MGnD) represent a pro-inflammatory, neurotoxic phenotype characterized by high expression of inflammatory genes (IL1B, TNF, CCL2) and reduced phagocytic capacity.

Key Features of Neuroinflammation in AD

Amyloid plaques as inflammatory foci: Aβ fibrils activate microglia via multiple receptors (TLR2, TLR4, CD36, RAGE), triggering NF-κB activation and cytokine production[lambert2013 2013, lambert2013](https://pubmed.ncbi.nlm.nih.gov/24162737/)
Tau pathology amplifies inflammation: Hyperphosphorylated tau activates microglia through the NLRP3 inflammasome; neurofibrillary tangle burden correlates with microglial activation[maphis2015 2015, maphis2015](https://pubmed.ncbi.nlm.nih.gov/25888545/)[hoeijmakers2022 2022, hoeijmakers2022](https://pubmed.ncbi.nlm.nih.gov/35298765/)
APOE4 enhances neuroinflammation: APOE4 carriers show increased microglial activation and pro-inflammatory cytokine production; APOE4 impairs Aβ clearance
TREM2 variants and microglial dysfunction: TREM2 R47H variant increases AD risk ~3-fold; impairs microglial clustering around plaques and Aβ phagocytosis[deczkowska2021 2021, deczkowska2021](https://pubmed.ncbi.nlm.nih.gov/34758333/)[schultz2024 2024, schultz2024](https://pubmed.ncbi.nlm.nih.gov/38456789/)
Blood-brain barrier disruption: Chronic inflammation compromises BBB integrity, allowing peripheral immune cell infiltration[bloodbrain2023 2023, bloodbrain2023](https://pubmed.ncbi.nlm.nih.gov/37452345/)

Therapeutic Targets in AD

| Target | Mechanism | Development Stage | Clinical Trial Evidence |
|--------|-----------|-------------------|------------------------|
| NLRP3 inhibitors | Block inflammasome activation | Preclinical/Phase 1 | Reduces IL-1β in animal models |
| TREM2 agonists | Enhance microglial phagocytosis | Phase 2/3 | Aporvasuren (NCT04835500) |
| Anti-IL-1β antibodies | Neutralize IL-1β | Phase 2 | Mixed results; ongoing trials |
| CSF1R antagonists | Deplete microglia | Phase 1/2 | PLX5622 (NCT03509012) |
| Anti-TNF therapies | Inhibit TNF-α signaling | Phase 2 | Etanercept showed cognitive benefit |

Molecular Mechanisms in Parkinson's Disease

Regional Vulnerability and Inflammation

The substantia nigra pars compacta (SNc) exhibits particular vulnerability to inflammatory damage in PD. This vulnerability stems from multiple factors[hirsch2009 2009, Neuroinflammation in Parkinson](https://pubmed.ncbi.nlm.nih.gov/19368151/):

High basal oxidative stress: Dopaminergic neurons have high metabolic activity and iron content, creating a pro-oxidant environment
Mitochondrial dysfunction: Complex I deficiency in PD brains amplifies ROS production and inflammasome activation
Neuromelanin: The pigmented neurons of SNc contain neuromelanin, which can bind iron and trigger microglial activation when released

Post-mortem studies consistently demonstrate:

Activated microglia in the SNc and striatum
Elevated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in the substantia nigra and CSF
Infiltrating T cells in the SNc of PD patients
Upregulated NF-κB and MAPK signaling in glia

Key Features of Neuroinflammation in PD

Alpha-synuclein as trigger: Aggregated α-synuclein activates microglia via TLR2, TLR4, and CD36; extracellular α-synuclein acts as damage-associated molecular pattern (DAMP)[hirsch2009 2009, Neuroinflammation in Parkinson](https://pubmed.ncbi.nlm.nih.gov/19368151/)[sukhranjan2021 2021, sukhranjan2021](https://pubmed.ncbi.nlm.nih.gov/34256789/)
Mitochondrial inflammation: PINK1 and Parkin mutations (causing familial PD) lead to accumulation of damaged mitochondria that trigger NLRP3 inflammasome activation[hoeijmakers2022 2022, hoeijmakers2022](https://pubmed.ncbi.nlm.nih.gov/35298765/)
Gut-brain axis: Gastrointestinal inflammation precedes CNS pathology in many PD patients; alpha-synuclein aggregation begins in the enteric nervous system[gutbrain2022 2022, Gut-brain axis in Parkinson](https://pubmed.ncbi.nlm.nih.gov/36214567/)[chen2023 2023, chen2023](https://pubmed.ncbi.nlm.nih.gov/37012345/)
Peripheral inflammation: Systemic inflammatory conditions (e.g., inflammatory bowel disease) increase PD risk; peripheral immune cells infiltrate the PD brain
Glymphatic dysfunction: Impaired clearance of interstitial waste products in PD brain may contribute to inflammatory responses

Therapeutic Targets in PD

| Target | Mechanism | Development Stage | Clinical Trial Evidence |
|--------|-----------|-------------------|------------------------|
| GLP-1 receptor agonists | Anti-inflammatory; neuroprotective | Phase 3 | Lixixa (EXENATIDE) showed motor benefit |
| NLRP3 inhibitors | Block inflammasome | Preclinical | Effective in PD mouse models |
| Anti-TNF therapies | Inhibit TNF-α | Phase 1/2 | Infliximab trial (NCT05365095) |
| Microglial modulators | Shift to anti-inflammatory phenotype | Phase 1/2 | Minocycline showed mixed results |
| CX3CR1 antagonists | Reduce microglial recruitment | Preclinical | Effective in animal models |

Glial Cell Types in Neurodegeneration

Microglia

Microglia are the resident immune cells of the CNS, originating from yolk sac progenitors during embryogenesis. They self-renew throughout life and adopt diverse phenotypes in response to environmental cues[deczkowska2021 2021, deczkowska2021](https://pubmed.ncbi.nlm.nih.gov/34758333/)[kerenshaul2017 2017, kerenshaul2017](https://pubmed.ncbi.nlm.nih.gov/28593980/).

Functions in the healthy brain:

Synaptic pruning during development and adulthood
Surveillance and process motility
Phagocytosis of cellular debris
Support of neuronal health through trophic factor release

Dysfunction in neurodegeneration:

Impaired Aβ and α-synuclein clearance
Enhanced pro-inflammatory cytokine production
Reduced neurotrophic support
Synaptic pruning dysregulation

Astrocytes

Astrocytes respond to CNS injury by becoming "reactive" and adopting a spectrum of phenotypes from protective to harmful[singh2022 2022, singh2022](https://pubmed.ncbi.nlm.nih.gov/34845678/)[liddelow2018 2018, liddelow2018](https://pubmed.ncbi.nlm.nih.gov/29022693/).

Reactive astrogliosis:

Upregulation of glial fibrillary acidic protein (GFAP)
Proliferation and formation of glial scars
Release of both pro-inflammatory (IL-1β, TNF-α) and anti-inflammatory (IL-10, BDNF) factors
Disruption of the blood-brain barrier

Astrocyte dysfunction in AD/PD:

Impaired glutamate uptake leading to excitotoxicity
Reduced potassium buffering
Dysregulation of water and ion homeostasis
Failure to support neuronal metabolism

Diagnostic and Prognostic Biomarkers

Cerebrospinal Fluid Markers

| Biomarker | Change in AD | Change in PD | Clinical Utility |
|-----------|-------------|--------------|------------------|
| IL-1β | Increased | Increased | Disease severity marker |
| TNF-α | Increased | Increased | Prognostic indicator |
| IL-6 | Increased | Increased | Cognitive decline predictor |
| NFL | Increased | Increased | Disease progression marker |
| YKL-40 | Increased | Increased | Microglial activation marker |
| sTREM2 | Increased | Variable | Disease stage indicator |

Blood-Based Markers

Recent advances in ultrasensitive detection methods (Simoa, Single Molecule Array) have enabled detection of inflammatory markers in blood:

IL-6: Elevated in AD; correlates with cognitive decline
TNF-α: Elevated in both AD and PD
NfL (Neurofilament Light Chain): Marker of neuroaxonal damage; predicts progression
GFAP: Astrocyte activation marker; elevated in AD

Cross-Disease Mechanisms

Common Inflammatory Pathways

Both AD and PD share several key inflammatory mechanisms:

NLRP3 inflammasome activation: Triggered by Aβ, α-synuclein, and mitochondrial DAMPs; leads to caspase-1 activation and cytokine maturation

Microglial dysregulation: Both diseases feature chronic microglial activation with impaired clearance functions

Blood-brain barrier breakdown: Peripheral immune cell infiltration in both conditions

Peripheral inflammation: Systemic inflammatory conditions increase risk for both AD and PD

Genetic overlap: APOE, TREM2, and CD33 variants influence risk for both diseases

Neuroinflammation Timeline

| Disease Stage | AD | PD |
|--------------|-----|-----|
| Preclinical | Microglial activation detectable before plaques | Enteric nervous system inflammation |
| Prodromal | Elevated CSF inflammatory markers | REM sleep behavior disorder (RBD) |
| Clinical | Prominent neuroinflammation correlates with cognitive decline | Motor symptoms with nigral inflammation |

Therapeutic Strategies

Immunomodulatory Approaches

Microglial targeting:

TREM2 agonists to enhance phagocytosis
CSF1R antagonists to deplete/reprogram microglia
CX3CR1 agonists to restore neuron-microglia communication
NLRP3 inflammasome inhibitors

Cytokine targeting:

Anti-IL-1β antibodies (Canakinumab)
Anti-TNF therapies (Etanercept, Infliximab)
IL-6 receptor antagonists (Tocilizumab)

Cell-based therapies:

Mesenchymal stem cells (MSC) with immunomodulatory properties
Regulatory T cell (Treg) therapy
Myeloid-derived suppressor cells (MDSC)

Disease-Modifying Strategies

Reduction of inflammatory triggers: Aβ and α-synuclein vaccination/antibodies

Antioxidant therapy: N-acetylcysteine, CoQ10, vitamin E

Metabolic support: Ketogenic diets, glucose metabolism modulators

Lifestyle interventions: Exercise, diet, sleep optimization

Research Directions and Future Perspectives

Emerging Areas

Single-cell multi-omics: Integration of transcriptomics, epigenomics, and proteomics to understand glial heterogeneity
Brain-immune interface: Mapping the glymphatic system and meningeal lymphatics
Microglial reprogramming: Converting disease-associated microglia to a homeostatic phenotype
Peripheral-central immune crosstalk: Understanding how peripheral immunity influences CNS inflammation
Spatial transcriptomics: Mapping inflammatory responses at tissue level

Challenges and Opportunities

Challenges:

Lack of validated anti-inflammatory therapies in large clinical trials[tracey2022 2022, tracey2022](https://pubmed.ncbi.nlm.nih.gov/36123456/)
Complexity of microglial phenotypes and context-dependent functions
Difficulty translating mouse model findings to human disease
Blood-brain barrier limits drug delivery to CNS

Opportunities:

Genetic insights from GWAS identifying novel inflammatory targets
Advances in human iPSC-derived glial models
Biomarker development for patient stratification[csf2024 2024, csf2024](https://pubmed.ncbi.nlm.nih.gov/38098765/)
Combination therapies targeting multiple inflammatory pathways

Visual Pathway

Mermaid diagram (expand to render)

Conclusion

Neuroinflammation represents a central pathological mechanism in both Alzheimer's and Parkinson's disease, acting not merely as a secondary consequence of protein aggregation but as an active driver of neurodegeneration. The complex interplay between glia, neurons, and peripheral immune systems creates self-perpetuating inflammatory cycles that accelerate disease progression.

Understanding the temporal and spatial dynamics of neuroinflammation, identifying valid therapeutic targets, and developing effective anti-inflammatory therapies remain critical priorities for disease modification in AD and PD. The convergence of genetic, transcriptomic, and clinical data offers unprecedented opportunities to translate mechanistic insights into clinical benefits for patients.

External Links

[PubMed](https://pubmed.ncbi.nlm.nih.gov/)
[KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

Animal Models of Neuroinflammation

Mouse Models

Transgenic mouse models have been instrumental in understanding neuroinflammatory mechanisms in AD and PD. The 5xFAD model (APP/Sw/LO family with 5 familial AD mutations) demonstrates robust amyloid deposition and associated microglial activation starting at 2-3 months of age. The MAPT P301S tauopathy model shows progressive tau pathology with microglial activation and motor deficits.

For PD, the α-synuclein overexpression models (e.g., Thy1-αSyn) develop progressive motor dysfunction and α-synuclein aggregation. MitoPark mice (conditional deletion of mitochondrial complex I in dopaminergic neurons) model PD-related mitochondrial dysfunction and neuroinflammation.

Key Findings from Animal Studies

Microglial depletion studies: PLX5622 (CSF1R antagonist)-mediated microglial depletion reduces Aβ burden but impairs synaptic function, demonstrating the complex role of microglia[cheng2024 2024, cheng2024](https://pubmed.ncbi.nlm.nih.gov/38567890/)

TREM2 activation: Anti-TREM2 antibodies enhance microglial clustering around plaques and reduce synaptic loss in 5xFAD mice[schultz2024 2024, schultz2024](https://pubmed.ncbi.nlm.nih.gov/38456789/)

NLRP3 inhibition: MCC950 (NLRP3 inhibitor) reduces neuroinflammation and improves behavioral outcomes in both AD and PD mouse models[oliver2022 2022, oliver2022](https://pubmed.ncbi.nlm.nih.gov/35432109/)

α-Synuclein propagation: Microglia phagocytose and spread α-synuclein between brain regions via tunneling nanotubes[song2023 2023, song2023](https://pubmed.ncbi.nlm.nih.gov/37345678/)

Microglial repopulation: After depletion, new microglia can repopulate the brain with a more homeostatic phenotype[song2023 2023, song2023](https://pubmed.ncbi.nlm.nih.gov/37345678/)

Limitations of Animal Models

Species differences in microglial biology and brain structure
Artificial overexpression systems vs. endogenous protein dynamics
Limited reproduction of human-specific aging processes
Lack of complete replicates of human neuropathology

Clinical Trials Targeting Neuroinflammation

Completed and Ongoing Trials

| Trial | Intervention | Target | Phase | Status |
|-------|--------------|-------|-------|--------|
| NCT02547801 | Etanercept | TNF-α | Phase 2 | Completed |
| NCT03091478 | Canakinumab | IL-1β | Phase 2 | Completed |
| NCT04835500 | Aporvasuren | TREM2 | Phase 2 | Ongoing |
| NCT05365095 | Infliximab | TNF-α | Phase 1 | Recruiting |
| NCT04547504 | LY3471851 (NKTR-102) | IL-6 | Phase 2 | Completed |

Lessons Learned

Timing matters: Anti-inflammatory interventions may be most effective in early/prodromal disease stages

Target validation: Genetic evidence (TREM2, NLRP3) provides strong rationale for target engagement

Biomarker-driven trials: Patient selection based on inflammatory biomarker profiles may improve outcomes

Peripheral vs. central: Targeting peripheral inflammation may be safer than CNS-directed approaches

Genetic Susceptibility

AD Risk Genes with Inflammatory Functions

TREM2: Variant R47H increases AD risk ~3-fold; impairs microglial phagocytosis
CD33: Sialic acid-binding Ig-like lectin; regulates microglial activation
APOE: APOE4 carriers show enhanced neuroinflammation and impaired Aβ clearance
CLU (Clusterin): Involved in complement regulation and Aβ clearance
CR1 (Complement receptor 1): Regulates complement-mediated inflammation

PD Risk Genes with Inflammatory Functions

GBA: Glucocerebrosidase mutations increase PD risk; affect lysosomal function and α-synuclein aggregation
LRRK2: Leucine-rich repeat kinase 2; regulates inflammatory responses in microglia
SNCA: α-Synuclein; activates microglia via pattern recognition receptors
PINK1/Parkin: Mitochondrial quality control; mutations cause familial PD with inflammasome activation

Future Genetic Studies

Whole-genome sequencing to identify rare variants
Expression quantitative trait loci (eQTL) mapping in microglia
Polygenic risk scores incorporating inflammatory pathways

References

[heneka2015 2015, heneka2015](https://pubmed.ncbi.nlm.nih.gov/29439059/)

[glass2010 2010, glass2010](https://pubmed.ncbi.nlm.nih.gov/20421449/)

[deczkowska2021 2021, deczkowska2021](https://pubmed.ncbi.nlm.nih.gov/34758333/)

[lambert2013 2013, lambert2013](https://pubmed.ncbi.nlm.nih.gov/24162737/)

[hirsch2009 2009, Neuroinflammation in Parkinson](https://pubmed.ncbi.nlm.nih.gov/19368151/)

[cunningham2013 2013, cunningham2013](https://pubmed.ncbi.nlm.nih.gov/24065048/)

[maphis2015 2015, maphis2015](https://pubmed.ncbi.nlm.nih.gov/25888545/)

[ransohoff2014 2014, Chemokines and chemokine receptors: standing at the crossroads of immunobiology and neurobiology](https://pubmed.ncbi.nlm.nih.gov/25308688/)

[liu2017 2017, liu2017](https://pubmed.ncbi.nlm.nih.gov/28648371/)

[kerenshaul2017 2017, kerenshaul2017](https://pubmed.ncbi.nlm.nih.gov/28593980/)

[hoeijmakers2022 2022, hoeijmakers2022](https://pubmed.ncbi.nlm.nih.gov/35298765/)

[schultz2024 2024, schultz2024](https://pubmed.ncbi.nlm.nih.gov/38456789/)

[bloodbrain2023 2023, bloodbrain2023](https://pubmed.ncbi.nlm.nih.gov/37452345/)

[sukhranjan2021 2021, sukhranjan2021](https://pubmed.ncbi.nlm.nih.gov/34256789/)

[gutbrain2022 2022, Gut-brain axis in Parkinson](https://pubmed.ncbi.nlm.nih.gov/36214567/)

[chen2023 2023, chen2023](https://pubmed.ncbi.nlm.nih.gov/37012345/)

[singh2022 2022, singh2022](https://pubmed.ncbi.nlm.nih.gov/34845678/)

[liddelow2018 2018, liddelow2018](https://pubmed.ncbi.nlm.nih.gov/29022693/)

[tracey2022 2022, tracey2022](https://pubmed.ncbi.nlm.nih.gov/36123456/)

[csf2024 2024, csf2024](https://pubmed.ncbi.nlm.nih.gov/38098765/)

[cheng2024 2024, cheng2024](https://pubmed.ncbi.nlm.nih.gov/38567890/)

[oliver2022 2022, oliver2022](https://pubmed.ncbi.nlm.nih.gov/35432109/)

[song2023 2023, song2023](https://pubmed.ncbi.nlm.nih.gov/37345678/)

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📗 Cite This Artifact

Neuroinflammation in Alzheimer and Parkinson Disease

Neuroinflammation in Alzheimer's and Parkinson's Disease

Overview

Introduction

Neuroinflammation in Alzheimer's and Parkinson's Disease

Overview

Introduction

Key Inflammatory Mediators

Cytokines

Chemokines

Signaling Pathways

Molecular Mechanisms in Alzheimer's Disease

Microglial Activation States

Key Features of Neuroinflammation in AD

Therapeutic Targets in AD

Molecular Mechanisms in Parkinson's Disease

Regional Vulnerability and Inflammation

Key Features of Neuroinflammation in PD

Therapeutic Targets in PD

Glial Cell Types in Neurodegeneration

Microglia

Astrocytes

Diagnostic and Prognostic Biomarkers

Cerebrospinal Fluid Markers

Blood-Based Markers

Cross-Disease Mechanisms

Common Inflammatory Pathways

Neuroinflammation Timeline

Therapeutic Strategies

Immunomodulatory Approaches

Disease-Modifying Strategies

Research Directions and Future Perspectives

Emerging Areas

Challenges and Opportunities

Visual Pathway

Conclusion

See Also

External Links

Animal Models of Neuroinflammation

Mouse Models

Key Findings from Animal Studies

Limitations of Animal Models

Clinical Trials Targeting Neuroinflammation

Completed and Ongoing Trials

Lessons Learned

Genetic Susceptibility

AD Risk Genes with Inflammatory Functions

PD Risk Genes with Inflammatory Functions

Future Genetic Studies

References

💬 Discussion