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Neurodegenerative Diseases Alzheimer’s Disease
production that is not restricted to the brain, but involves also the activation of signalling pathways that lead to further inflammation and
peripheral system, and that the administration of acetylcholinesterase neuronal injury, and both pharmacological and immunological tools
inhibitor (AchEI) downregulates IL-1, IL-6 and TNF-α and upregulates are now available to confirm or refute this.
the expression and production of IL-4.
23,24
This result may suggest that
inhibitors of AchE lead to the remodelling of the cytokine network, An interesting further question is whether or not systemic inflammation
probably acting on the lymphocyte cholinergic system. influences the progression of a chronic neurodegenerative disease,
or is simply a consequence of tissue degeneration. In order to account
Concluding Remarks for these different scenarios, two not mutually exclusive possibilities
Increasing evidence suggests that inflammation and alteration of the have been proposed. On the one hand, the overproduction of brain
cytokine–chemokine network contributes to the pathophysiology of cytokines may contribute to the pool of peripheral cytokines by a spill-
AD. The concomitant release of pro-inflammatory cytokines that over from the CNS, whereas on the other hand peripheral cytokines
influence neurodegenerative pathways and anti-inflammatory may affect brain functions by crossing the BBB and directly interacting
cytokines may contribute to the chronicity of the disease. It is the with CNS targets.
balance of pro-inflammatory and anti-inflammatory products that
may be essential in the degenerative process; influencing this balance In the end, however, the greatest potential to aid the development of
may help in slowing the disease. mechanistically driven treatments will likely derive from identifying
the crucial factors responsible for the detrimental neuroinflammatory
Although the interpretation of the results of many AD studies has responses that occur in neurodegenerative diseases. In this regard,
been somewhat controversial and confounded by limitations in promising results for neurological disease treatment may be derived
sampling, in general all demonstrated an activation of the peripheral by targeting cytokines and chemokines in the development of
immune status that was probably linked to an inflammatory condition antagonists and synthesis inhibitors. n
present in the brain. Assuming that the brain’s pathological events are
replicated in some manner in the periphery, it would seem rational to
Domenico Gambi is a Full Professor of Neurology and Chairman of the Department
propose a link between the cytokine profiles of the brain and the
of Oncology and Neuroscience at the University G D’Annunzio Chieti-Pescara.
systemic circulation. He was previously Chairman of the Institute of Neurology and Behavioral
Sciences at the same institution. He is also a member of the Council of Italian
Neurologic Collegium and holder of target research projects funded by the
Certainly the most important limitation of the majority of the research
Italian National Research Council. Professor Gambi is the author of many
reviewed is the acknowledged cross-sectional design of the studies, scientific publications mainly focusing on multiple sclerosis, Alzheimer’s
from which it is not possible to define any ‘cause–effect relationship’.
disease and Parkinson’s disease.
In particular, such studies cannot distinguish whether or not high
Marcella Reale is a Physician in the Unit of Immunodiagnostics in the Department
cytokine levels might contribute to the pathogenesis of AD or
of Oncology and Neuroscience at the University G D’Annunzio Chieti-Pescara. Her
represent a protective response. The two are not mutually exclusive, primary research interests include the characterisation of functional and
and could be time-, location- and concentration-dependent.
immunological activation of peripheral blood mononuclear cells (PBMC) from
patients with neurodegenerative disease, measuring production of cyto-
Moreover, dementia may lead to high cytokine levels, or other as yet
chemokines and their activation pathways. She is a member of the Editorial Board
unknown factors may contribute to both cognitive impairment and of the Journal of Alzheimer's Disease and the International Journal of Alzheimer’s
systemic inflammation. Although the precise molecular and cellular
Disease. Dr Reale is the author of many scientific publications, mainly on multiple
sclerosis, Alzheimer’s disease and Parkinson’s disease.
relationship between neurodegeneration and inflammation remains
ambiguous, there is strong evidence that cytokines may induce
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