Insights on the pathophysiology of Alzheimer's disease: The crosstalk between amyloid pathology, neuroinflammation and the peripheral immune system
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Alzheimer's disease (AD) is the most common form of dementia, whose prevalence is growing along with the increased life expectancy. Although the accumulation and deposition of amyloid beta (Aβ) peptides in the brain is viewed as one of the pathological hallmarks of AD and underlies, at least in part, brain cell dysfunction and behavior alterations, the etiology of this neurodegenerative disease is still poorly understood. Noticeably, increased amyloid load is accompanied by marked inflammatory alterations, both at the level of the brain parenchyma and at the barriers of the brain. However, it is debatable whether the neuroinflammation observed in aging and in AD, together with alterations in the peripheral immune system, are responsible for increased amyloidogenesis, decreased clearance of Aβ out of the brain and/or the marked deficits in memory and cognition manifested by AD patients. Herein, we scrutinize some important traits of the pathophysiology of aging and AD, focusing on the interplay between the amyloidogenic pathway, neuroinflammation and the peripheral immune system.
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At 15 months, intense pathology is present in the TG mice, including Aβ plaques, tau, myelin damage, axonal degeneration, axonal loss, and an inflammatory reaction with reactive microglia and astrocytes.
“At 15 months, intense pathology is present in the TG mice, which includes not only Aβ plaques and tau, but also confounding factors, such as, myelin damage, axonal degeneration, axonal loss, and an inflammatory reaction with reactive microglia and astrocytes [29, 30].”
From Brain microstructure abnormalities in the 3xTg-AD mouse – A diffusion MRI and morphology correlation study (2022) · cites this paper as [30]
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- Authors
- Dá Mesquita, S., Ferreira, A. C., Sousa, J. C., Correia-Neves, M., Sousa, N., & Marques, F.
- Affiliations
- University of Minho (PT)
- Corresponding author
- Marques, Fernanda
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 68
- Pages
- 547-562
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W2424200948
- Cited by
- 166
- References
- 56
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 15 · 2023: 29 · 2022: 11 · 2021: 15 · 2020: 16 · 2019: 17 · 2018: 18 · 2017: 24 · 2016: 1
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- RepositóriUM (Universidade do Minho) (submittedVersion, other-oa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by-nc-nd)
- Funders
- FCT and COMPETE
- Bial Foundation (217/12)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid-beta, neuroinflammation, peripheral immune system, aging, amyloidogenesis, amyloid clearance, blood-brain barrier, neurodegeneration, memory impairment
- MeSH terms
- Aging, Alzheimer Disease, Brain, Humans, Immune System, Amyloid beta-Peptides
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