Neuroinflammation in Alzheimer's Disease and Parkinson's Disease: Are Microglia Pathogenic in Either Disorder?
Abstract
Microglial activation similar to that which occurs in peripheral macrophages during inflammatory attack was first demonstrated in the Alzheimer's disease (AD) brain two decades ago. Localization to pathologically vulnerable regions of AD cortex, localization to sites of specific AD pathology such as amyloid-beta peptide (Abeta) deposits, and the ability of activated microglia to release toxic inflammatory factors suggested that the activation of microglia in AD might play a pathogenic role. However, proving this hypothesis in a disease in which so many profound pathologies occur (e.g., Abeta deposition, neurofibrillary tangle formation, inflammation, neuronal loss, neuritic loss, synaptic loss, neuronal dysfunction, vascular alterations) has proven difficult. Although investigations of microglia in Parkinson's disease (PD) are more recent and therefore less extensive, demonstration of a pathogenic role for microglial activation may actually be much simpler in PD than AD because the root pathological event in PD, loss of dopamine (DA)-secreting substantia nigra neurons, is already well established. Indeed, indirect but converging evidence of a pathogenic role for activated microglia in PD has already begun to emerge. The nigra reportedly has the highest density of microglia in brain, and, in PD, nigral microglia are not only highly activated but also highly clustered around dystrophic DA neurons. 6-OHDA and MPTP models of PD in rodents induce substantia nigra microglial activation. More cogent, injections of the classic microglial/macrophage activator lipopolysaccharide into or near the rodent nigra cause a specific loss of DA neurons there. Culture models with human microglia and human cellular targets replicate this phenomenon. Notably, nearly all the proposed etiologies of PD, including brain bacterial and viral exposure, pesticides, drug contaminants, and repeated head trauma, are known to cause brain inflammation. A mechanism by which activated microglia might specifically target DA neurons remains a critical missing link in the proof of a pathogenic role for activated microglia in PD. If such a link could be established, however, clinical intervention trials with agents that dampen microglial activation might be warranted in PD.
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The deposition of Aβ and α-syn activates microglia in the brain and triggers neuroinflammation, which leads to memory and cognitive impairment in AD patients and motor and non-motor symptoms in PD patients.
“The deposition of Aβ and α-syn activates microglia in the brain and triggers neuroinflammation, which leads to memory and cognitive impairment in AD patients and motor and non-motor symptoms in PD patients (Rogers et al. 2007).”
From Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease (2020) · cites this paper as Rogers et al. 2007
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- Authors
- Rogers, J., Mastroeni, D., Leonard, B., Joyce, J., & Grover, A.
- Affiliations
- Banner Sun Health Research Institute (US)
- Venue
- International Review of Neurobiology
- Publisher
- Elsevier
- Published
- 2007
- Volume
- 82
- Pages
- 235-246
- ISSN
- 0074-7742 (ISSN-L)
- OpenAlex
- W1565096249
- Cited by
- 260
- References
- 41
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 7 · 2023: 3 · 2022: 12 · 2021: 14 · 2020: 13 · 2019: 15 · 2018: 13 · 2017: 18 · 2016: 12 · 2015: 16 · 2014: 23 · 2013: 12 · 2012: 18
- FWCI
- 33.00
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- International review of neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- neuroinflammation, microglial activation, Alzheimer's disease, Parkinson's disease, amyloid-beta, neurofibrillary tangles, substantia nigra, dopamine neuron loss, lipopolysaccharide, MPTP, 6-hydroxydopamine, neurodegeneration
- MeSH terms
- Alzheimer Disease, Animals, Cells, Cultured, Humans, Inflammation, Nervous System Diseases, Parkinson Disease, Microglia
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