Download Immunology and Alzheimer`s disease

The role of immune system in Alzheimer’s disease
Dorotea Muck Seler
Division of Molecular Medicine, R. Boskovic Institute, HR-10000 Zagreb, Croatia
Alzheimer’s disease (AD) is a complex, multifactorial and progressive neurodegenerative disorder.
Recent studies suggest that immune system plays an important role in the neurodegenerative
processes (1). Microglia and astrocytes are key brain neuroglial cells that regulate two opposite i.e.
protective and harmful effects of immune system on neurodegeneration.
Microglia are brain macrophages/phagocytes that remove and clear fragments of damaged or dead
cells (2). In the normal aging and in the early stage AD microglia have neuroprotective role by
contributing to the clearance of amyloid-beta (A) aggregates and neurofibrillary tangle formation, and
stimulation of anti-inflammatory cytokines (IL-4, IL-10). The age-related changes and progressive
accumulation of AD specific pathological elements induce chronic activation of microglia in an attempt
to remove these pathological structures. Activated microglia release pro-inflammatory cytokines (IL-1,
IL-6, TNF-) and other neurotoxic proteins that further stimulate inflammatory process and contribute
to neuronal dysfunction and neurodegeneration (3).
Astrocytes are component of the tripartite synapse that mediates connectivity between neuronal and
non-neuronal cells and regulate extracellular homeostasis of ions and neurotransmitters. The
perisynaptic astrocytes remove the majority of excitatory neurotransmitter glutamate from extracellular
space and prevent its neurotoxic effect. The studies in transgenic animal model of AD suggest that
astrocytic atrophy and astrogliosis are associated with development of AD. At the later stages of
disease, astrocytes become activated and contribute to the neuroinflammatory component of
neurodegeneration (4).
Although cytokines represent the important component of neuroinflammation in AD, the analysis of
genotype and allele frequencies of IL-1, IL-6, IL10 and TNF- gene polymorphisms did not show
significant difference between patients with AD and healthy controls.
In summary recent data suggest that neuroinflammatory processes and altered function of the brain
innate immune cells represent important etiological risk factor for the development and progress of
AD. Targeting neuroinflammation and immune system might be an attractive new therapeutic
approach in the treatment of AD.
References
1. Weiner H, Frenkel D. Immunology and immunotherapy of Alzheimer’s disease. Nat Rev
Immunol, 2006, 6:404-417.
2. Solito E , Sastre M. Microglia function in Alzheimer’s disease. Frontiers in Pharmacology 2012,
3:1-10.
3. Guillot-Sestier M-V, Town T. Innate immunity in Alzheimer’s disease: a complex affair. CNS
Neurol Disord Drug Targets 2013, 12:293-607.
4. Heneka MT, Rodriguez JJ, Verkhratsky. Neuroglia in neurodegeneration. Brain Res Review,
2010, 63:189-211.