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Advanced Neurology Antibodies as neurodegenerative biomarkers

compartments, cerebral spinal fluid (CSF), and the choroid the various barriers that restrict the entry and exit of
plexus house substantial immune cell populations, immune cells into and out of the brain. However, the
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6-8
establishing them as true immune niches. These revelations immune system is active in the CNS and shows different
underscore a close crosstalk between the CNS and the characteristics in central and peripheral regions. In this
immune system, extending beyond pathological processes. sense, both the graft rejection observed in the CNS 21,22 and
However, this close relationship has adverse implications, the ability of activated T cells to cross the BBB, even in
particularly concerning aging and neurodegenerative the absence of neuroinflammation, underscore the active
4
diseases such as Alzheimer’s disease (AD) or Parkinson’s nature of the immune system within the CNS.
disease (PD), among others. 9,10
The anatomical location of the CNS, within the skull
According to recent research, the adaptive immune and vertebral column, provides protection from infections
system plays a pivotal role in AD, although the apparent and injuries. The CNS is also protected by barriers such
controversy among the findings suggests that its as the leptomeningeal blood-CSF barrier, the glia limitans,
involvement is complex. Patients with AD exhibit elevated the endothelial BBB, and the blood-CSF barrier of the
levels of CD8+ T cells in the CSF, accompanied by the choroid plexus that regulate access not only to pathogens
coexistence of amyloid beta (Aβ) plaques. 11,12 Animal but also to immune cells from the periphery. 23
studies reveal that certain CD4+ T cell subpopulations, The meningeal layer is a structure surrounding the
mainly Th17 cells, release inflammatory cytokines, brain and spinal cord, consisting of three layers: the
exacerbating AD progression, while another subset, Type 1 dura mater, the arachnoid mater, and the pia mater.
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regulatory T cells, curtails their secretion. 13,14 B cells also The dura mater has blood vessels lacking BBB and
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play an important role in aging and neurodegeneration. lymphatic vessels to drain antigens and immune cells
Reactive autoantibodies against brain and non-brain from the CNS. 25,26 The arachnoid mater restricts solute
antigens have been identified in patients with AD and diffusion and expresses efflux pumps to remove harmful
other pathologies as subacute sclerosing panencephalitis metabolites from the CSF. 27,28 The pia mater allows solute
and post-encephalitic parkinsonism. Notably, antibodies permeation while impeding cellular passage such as
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directed against Aβ can ameliorate the toxicity of erythrocytes. 28,29
Aβ oligomers and protofibrils, promote microglial
phagocytosis, and improve cognitive performance. 16 The glia limitans consist of a basal membrane created by
astrocytes, which extensively covers the surface of the brain
In PD, adaptive immunity gains relevance at disease and spinal cord, acting as a barrier. It prevents migratory
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onset; yet, further research is imperative to elucidate immune cells from freely accessing the subarachnoid and
whether it exerts a neuroprotective role or, on the contrary, perivascular spaces, thus maintaining controlled access to
contributes to degeneration. T cell reactivity to alpha- the CNS parenchyma. 30,31
synuclein (α-syn) occurs especially in the initial stages of
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motor symptoms. In postmortem brain tissue from PD The BBB serves as a highly effective barrier between
patients, CD4+ and CD8+ T, but not B cells, have been the bloodstream and the CNS. It is composed of brain
reported in the substantia nigra. Nevertheless, anti- microvascular endothelial cells with continuous and
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α-syn antibodies and autoantibodies can be detected in complex tight junctions, preventing unrestricted
fluids from patients with genetic and sporadic forms of the movement of solutes and water-soluble molecules
disease. Moreover, proinflammatory interleukins secreted between the blood and the CNS. 32,33 The BBB, along
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during PD have also been associated with accelerated with the blood-nerve barrier, protects the CNS and the
motor deterioration. 20 peripheral nervous system, respectively, from the entry
of antibodies, T cells, and other toxic constituents of the
Hence, this review aims to delve into recent findings plasma (Figure 1A).
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on the intricate relationship between the immune system
and CNS homeostasis, primarily focusing on the adaptive The blood-CSF barrier of the choroid plexus is
immune response and its impact on neurodegenerative epithelial-endothelial vascular convolute found in all four
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diseases. In addition, it explores the role of reactive brain ventricles. Their cells produce CSF and prevent
antibodies in these diseases, emphasizing their potential as substances from diffusing across the blood and CSF
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diagnostic biomarkers. through tight junctions. The choroid plexus stroma
also serves as a habitat for immune cells, suggesting its
2. Immune systems in the brain significance in the immunological defense of the CNS. 37
It was long believed that the CNS was resistant to immune Neurodegenerative diseases, marked by significant
system activity due to the lack of lymphatic vessels and neuronal loss, reactive gliosis, and abnormal protein

Volume 3 Issue 1 (2024) 2 https://doi.org/10.36922/an.2058