Abstract
According to the current paradigm, the main cause of AD is the accumulation of neurotoxic amyloid beta (Aβ) peptide aggregates resulting from the cleavage of the amyloid precursor protein into peptides of different length, with the 42 amino acid long Aβ42 being the most toxic form. Aβ can aggregate and form plaques in the brain. It further promotes the hyperphosphorylation of the tau protein which forms characteristic neurofibrillary tangles and thereby loses its important role in axonal transport and contributes to neurodegeneration. Therefore, treatments have targeted Aβ, but clinical trials of immunotherapies caused severe side effects and showed that Aβ clearance alone did not result in any cognitive improvement. This leads to the question: what else promotes AD pathology? Here, we review data on systemic inflammation and the possible roles that the immune system might play in AD. Microglia and astrocytes are activated and secrete inflammatory cytokines and chemokines. Via a disturbed blood-brain barrier, peripheral immune cells are activated and recruited towards inflamed brain lesions and amyloid plaques, but due to the chronic nature of the amyloid burden and their reduced function, these cells are not able to control inflammation and the associated detrimental immune responses. In addition, age-related inflammation and chronic infection with herpes viruses might contribute to the systemic inflammation and exacerbate attempts to restore the balance of inflammation.
Keywords: Alzheimer Disease, CMV, HSV, immunity, Inflammation, leukocytes, T-cell differentiation.
Current Alzheimer Research
Title:Peripheral Immune Signatures in Alzheimer Disease
Volume: 13 Issue: 7
Author(s): David Goldeck, Jacek M. Witkowski, Tamas Fülop and Graham Pawelec
Affiliation:
Keywords: Alzheimer Disease, CMV, HSV, immunity, Inflammation, leukocytes, T-cell differentiation.
Abstract: According to the current paradigm, the main cause of AD is the accumulation of neurotoxic amyloid beta (Aβ) peptide aggregates resulting from the cleavage of the amyloid precursor protein into peptides of different length, with the 42 amino acid long Aβ42 being the most toxic form. Aβ can aggregate and form plaques in the brain. It further promotes the hyperphosphorylation of the tau protein which forms characteristic neurofibrillary tangles and thereby loses its important role in axonal transport and contributes to neurodegeneration. Therefore, treatments have targeted Aβ, but clinical trials of immunotherapies caused severe side effects and showed that Aβ clearance alone did not result in any cognitive improvement. This leads to the question: what else promotes AD pathology? Here, we review data on systemic inflammation and the possible roles that the immune system might play in AD. Microglia and astrocytes are activated and secrete inflammatory cytokines and chemokines. Via a disturbed blood-brain barrier, peripheral immune cells are activated and recruited towards inflamed brain lesions and amyloid plaques, but due to the chronic nature of the amyloid burden and their reduced function, these cells are not able to control inflammation and the associated detrimental immune responses. In addition, age-related inflammation and chronic infection with herpes viruses might contribute to the systemic inflammation and exacerbate attempts to restore the balance of inflammation.
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Cite this article as:
Goldeck David, M. Witkowski Jacek, Fülop Tamas and Pawelec Graham, Peripheral Immune Signatures in Alzheimer Disease, Current Alzheimer Research 2016; 13 (7) . https://dx.doi.org/10.2174/1567205013666160222112444
DOI https://dx.doi.org/10.2174/1567205013666160222112444 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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