The DOI matches its Crossref record; 283 of the 283 references it cites were found in a registry or an index.
Inflammation as a central mechanism in Alzheimer's disease
Open accessAbstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by cognitive decline and the presence of two core pathologies, amyloid β plaques and neurofibrillary tangles. Over the last decade, the presence of a sustained immune response in the brain has emerged as a third core pathology in AD. The sustained activation of the brain's resident macrophages (microglia) and other immune cells has been demonstrated to exacerbate both amyloid and tau pathology and may serve as a link in the pathogenesis of the disorder. In the following review, we provide an overview of inflammation in AD and a detailed coverage of a number of microglia‐related signaling mechanisms that have been implicated in AD. Additional information on microglia signaling and a number of cytokines in AD are also reviewed. We also review the potential connection of risk factors for AD and how they may be related to inflammatory mechanisms.
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In the citing paper
“Numerous cytokines and chemokines have been shown to contribute to the pathogenesis of neurodegenerative diseases as summarized by the recent reviews.9,253,412”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This immune response in turn activates glia and induces the secretion of pro-inflammatory cytokines, which can drive further aggregation of Aβ by affecting the capacity of microglia and astrocytes for phagocytosis and degradation [26].”
From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [26]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Chronic microglial inflammation has been observed in the brains of AD patients at various disease stages, and pro-inflammatory cytokines such as IL-1β, IL-2, IL-6, and tumor necrosis factor-α have been shown to be upregulated in AD [35].”
From Cerebrospinal fluid levels of the neurotrophic factor neuroleukin are increased in early Alzheimer’s disease, but not in cerebral amyloid angiopathy (2021) · cites this paper as [35]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Aβ levels are generally well-correlated with immune activation indicated by microgliosis and astrocytosis [3].”
From Deletion of Abi3/Gngt2 influences age-progressive amyloid β and tau pathologies in distinctive ways (2022) · cites this paper as [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Currently, the innate immune system activation, in particular microglia, is considered a contributing factor to AD pathogenesis rather than a consequence of pathology 2 .”
From ABI3 deletion in TgCRND8 mice is associated with reduced amyloid plaque pathology and altered glial response (2023) · cites this paper as [2]
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In the citing paper
“Theses neuroinflammatory responses are considered a major driving factor in patients with neurodegeneration and Alzheimer’s disease pathology, which starts early in the course of the disease, prior to the formation of Aβ plaques in the brain73.”
From Chlamydia pneumoniae can infect the central nervous system via the olfactory and trigeminal nerves and contributes to Alzheimer’s disease risk (2022) · cites this paper as [73]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the comparison between B6 and 5xFAD mice, the concentrations of two proinflammatory cytokines, interleukin-1 β (IL-1B), tumor necrosis factor-alpha (TNFα ), were increased Figure 3G), and those of two other cytokines, IL-10, IL-5, were decreased (Figure 3H), consistent with previous findings 30 .”
From Genetic variants of phospholipase C-γ2 alter the phenotype and function of microglia and confer differential risk for Alzheimer’s disease (2023) · cites this paper as [30]
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In the citing paper
“Prolonged microglial activation may be detrimental, since it eventually leads to a self-perpetuating cycle involving the production of neurotoxic pro-inflammatory cytokines, damaging neurons, inducing more recruitment of microglia, further increasing their activation and release of pro-inflammatory cytokines [35].”
From Cerebrospinal fluid levels of the neurotrophic factor neuroleukin are increased in early Alzheimer’s disease, but not in cerebral amyloid angiopathy (2021) · cites this paper as [35]
The cited source says what the claim attributes to it.
In the citing paper
“Neuroinflammation is also linked to neurodegeneration and neuronal loss, which are features that coincidently are associated with amyloid plaque formation (DeTure and Dickson, 2019; Kinney et al., 2018; Sung et al., 2020).”
From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Kinney et al., 2018
In the citing paper
“Due to the dysregulation of GABAergic mechanism in AD, the inhibitory role of GABA on activated microglia is also lost which further contributes to the release of pro-inflammatory cytokines [17].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [17]
In the citing paper
“The chronic, sustained inflammatory response in the brain is considered the third core pathological feature of AD.”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [84]
In the citing paper
“This chronic neuroinflammation is caused by persistent activation of glial cells and excessive release of cytotoxic molecules, which adversely affects brain function and is a major cofactor in the pathogenesis of many neurodegenerative disorders, including AD [84].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [84]
In the citing paper
“It provides a link between the other two core pathologies, Aβ plaques and NFTs [84].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [84]
In the citing paper
“Continuous activation of the brain’s immune cells, such as microglia, leads to the release and production of various proinflammatory cytokines, which aids tau and Aβ pathologies and leads to the loss of neurons [24].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [24]
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Citations
Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · cited 2×
“[144] Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al.”
BackgroundGlutamate neurotoxicity and diseases of the nervous system
Choi, D. W. (1988) · Neuron · doi:10.1016/0896-6273(88)90162-6 · Cited by 8,188
Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518 · cited 2×
“[261] Hotamisligil GS, Shargill NS, Spiegelman BM.”
BackgroundA Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514
Hearing loss and cognitive decline in older adults
Lin, F. R., Yaffe, K., Xia, J., Xue, Q.-L., Harris, T. B., Purchase-Helzner, E., Satterfield, S., Ayonayon, H. N., Ferrucci, L., Simonsick, E. M., et al. (2013) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2013.1868 · Cited by 4,017
ATP mediates rapid microglial response to local brain injury in vivo
Davalos, D., Grutzendler, J., Yang, G., Kim, J. V., Zuo, Y., Jung, S., Littman, D. R., Dustin, M. L., & Gan, W.-B. (2005) · Nature Neuroscience · doi:10.1038/nn1472 · Cited by 3,913 · cited 2×
“Overall surveillance of the surrounding neuronal environment is accomplished via a large number of signaling mechanisms [99,102].”
BackgroundAssociation of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786
Flagged first, then by citations
Research works printed but not linked: 3
- Alzheimer's Impact Movement, 2017, Alzheimer's Disease Caregivers Factsheet
- 10.1186/1750-1326-9-20 · DOI · Paper page
- 10.1186/s13024-017-0216-6 · DOI · Paper page
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Vasileva, L. A., Gaynanova, G. A., Romanova, E. A., Petrov, K. A., Feng, C., Zakharova, L. Y., & Sinyashin, O. G. (2024) · Russian Chemical Reviews · doi:10.59761/rcr5150 · Cited by 15
Martá-Ariza, M., Leitner, D. F., Kanshin, E., Suazo, J., Giusti Pedrosa, A., Thierry, M., Lee, E. B., Devinsky, O., Drummond, E., Fortea, J., et al. (2025) · Acta Neuropathologica · doi:10.1007/s00401-025-02844-z · Cited by 15
Kjeldsen, E. W., Thomassen, J. Q., Rasmussen, K. L., Nordestgaard, B. G., Tybjærg-Hansen, A., & Frikke-Schmidt, R. (2022) · Epidemiology and Psychiatric Sciences · doi:10.1017/s2045796022000567 · Cited by 13
Transcriptomic predictors of rapid progression from mild cognitive impairment to Alzheimer's disease
Huang, Y.-L., Tsai, T.-H., Shen, Z.-Q., Chan, Y.-H., Tu, C.-W., Tung, C.-Y., Wang, P.-N., & Tsai, T.-F. (2025) · Alzheimer's Research & Therapy · doi:10.1186/s13195-024-01651-0 · Cited by 13
De Kort, A. M., Kuiperij, H. B., Alcolea, D., Kersten, I., Versleijen, A. A. M., Greenberg, S. M., Stoops, E., Schreuder, F. H. B. M., Klijn, C. J. M., Lleó, A., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00899-0 · Cited by 13
Fongsaran, C., Jirakanwisal, K., Peng, B.-H., Fracassi, A., Taglialatela, G., Dineley, K. T., Paessler, S., & Cisneros, I. E. (2024) · Brain, Behavior, & Immunity - Health · doi:10.1016/j.bbih.2024.100780 · Cited by 9
“Neuroinflammation is also linked to neurodegeneration and neuronal loss, which are features that coincidently are associated with amyloid plaque formation (DeTure and Dickson, 2019; Kinney et al., 2018; Sung et al., 2020).”
BackgroundNon-invasive in vivo imaging of brain and retinal microglia in neurodegenerative diseases
Etebar, F., Harkin, D. G., White, A. R., & Dando, S. J. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1355557 · Cited by 7
Ghaffari, D., Griffin, J., & St George-Hyslop, P. (2023) · doi:10.1101/2023.10.05.560956 · Cited by 3
“In support of these observations, here we show that ABI3 immunoreactivity (red) is mainly localized to Iba-1 positive microglia/macrophages (green) in two hippocampal regions (Dentate Gyrus [ Figure 1.”
Influential
Metadata
- Authors
- Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T.
- Affiliations
- University of Nevada, Las Vegas (US)
- Indiana University Indianapolis (US)
- Department of Psychology University of Nevada Las Vegas Las Vegas NV USA
- Corresponding author
- Kinney, Jefferson W.
- ORCID
- Lamb, Bruce T.
- Venue
- Alzheimer's & Dementia: Translational Research & Clinical Interventions
- Publisher
- Wiley
- Published
- 2018-01
- Volume
- 4
- Issue
- 1
- Pages
- 575-590
- ISSN
- 2352-8737 (ISSN-L)
- PMC
- PMC6214864
- OpenAlex
- W2889787710
- Cited by
- 2,253
- References
- 283
- Citations by year
- 2026: 187 · 2025: 395 · 2024: 401 · 2023: 353 · 2022: 326 · 2021: 286 · 2020: 226 · 2019: 76 · 2018: 1
- FWCI
- 13.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia Translational Research & Clinical Interventions (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Scholarship - UNLV (University of Nevada Reno) (submittedVersion, cc-by-nd)
- Digital Scholarship - UNLV (University of Nevada Reno) (submittedVersion, cc-by-nc-nd)
- IUScholarWorks (Indiana University) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (P20GM109025)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, neuroinflammation, microglia, amyloid plaques, neurofibrillary tangles, tau pathology, cytokines, risk factors, neurodegeneration
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