Peripheral immune system in aging and Alzheimer’s disease
Open accessAbstract
Alzheimer's disease (AD) represents an urgent public health mandate. AD is no longer considered a neural-centric disease; rather, a plethora of recent studies strongly implicate a critical role played by neuroinflammation in the pathogeneses of AD and other neurodegenerative conditions. A close functional connection between the immune system and central nervous system is increasingly recognized. In late-onset AD, aging represents the most significant risk factor. Here, from an immunological perspective, we summarize the prominent molecular and cellular changes in the periphery of aging individuals and AD patients. Moreover, we review the knowledge gained in the past several years that implicate specific arms of the peripheral immune system and other types of immune responses in modulating AD progression. Taken together, these findings collectively emphasize a dynamic role of a concert of brain-extrinsic, peripheral signals in the aging and degenerative processes in the CNS. We believe that a systematic view synthesizing the vast amounts of existing results will help guide the development of next-generation therapeutics and inform future directions of AD investigation.
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There is a positive correlation between levels of circulatory inflammatory molecules and progression of neurodegenerative diseases.
“Studies demonstrate a positive correlation between levels of circulatory inflammatory molecules and the progression of neurodegenerative diseases. 95 , 96”
From Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies (2024) · cites this paper as [95]
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Ageing as a risk factor for neurodegenerative disease
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Periodontal microorganisms and Alzheimer disease – A causative relationship?
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Aging and Neurodegenerative Disease: Is the Adaptive Immune System a Friend or Foe?
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Genetic determinants of survival in progressive supranuclear palsy: a genome-wide association study
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Plasma Markers of Inflammation Linked to Clinical Progression and Decline During Preclinical AD
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Control of the temporal development of Alzheimer’s disease pathology by the MR1/MAIT cell axis
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“Although neuroinflammation facilitates a significant amount of brain pathology in AD, there is still very little known about how the immune system plays a role [2, 37, 38].”
BackgroundStaley, H. A., Jernigan, J. E., Bolen, M. L., Titus, A. M., Neighbarger, N., Cole, C., Menees, K. B., Wallings, R. L., & Tansey, M. G. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03271-9 · Cited by 9 · see citing works
“The lack of disease-modifying interventions for AD until recently has fueled the search for identification of dysregulated immune pathways as potential new targets to delay, arrest, and perhaps prevent disease development [6].”
BackgroundThe transcriptional and cellular landscape of cognitive resilience to Alzheimer’s disease
Khera, N., Raju, R. M., & Lipton, S. A. (2025) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2025.1665802 · Cited by 3 · see citing works
- Authors
- Cao, W., & Zheng, H.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Cao, Wei
- Zheng, Hui
- ORCID
- Venue
- Molecular Neurodegeneration
- Published
- 2018-10-03
- Volume
- 13
- Issue
- 1
- Pages
- 51-51
- ISSN
- 1750-1326 (ISSN-L)
- PMC
- PMC6169078
- OpenAlex
- W2894696369
- Cited by
- 214
- References
- 199
- Citations by year
- 2026: 14 · 2025: 18 · 2024: 30 · 2023: 34 · 2022: 34 · 2021: 30 · 2020: 33 · 2019: 19 · 2018: 2
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-10-24)
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Neurodegeneration (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (AG020670)
- National Institute on Aging (RF1AG054111, RF1AG057587, RF1AG020670, R01AG032051, R01AG020670)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, aging, peripheral immune system, neuroinflammation, neurodegeneration, late-onset Alzheimer's disease, immunomodulation
- MeSH terms
- Aging, Alzheimer Disease, Animals, Behavior, Central Nervous System, Disease Models, Animal, Humans, Immune System
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