Abstract
Neuroinflammation and brain functional disconnection result from β-amyloid (Aβ) accumulation and play fundamental roles in the pathogenesis of Alzheimer’s disease (AD). We investigated possible correlations between these two AD-associated phenomena using DTI-based tractography and immunologic analyses in people with amnestic mild cognitive impairment (aMCI) and AD. DTI-Analyses focused on corpus callosum (CC). We found that frontal CC regions were preserved with respect to the posterior ones in aMCI; in these individuals significant correlations were seen between DTI-derived metrics in frontal-parietal CC areas and Aβ42-stimulated BDNF-producing CD4+ T lymphocytes and PDL-1-expressing CD14+ cells. These associations were lost in AD where DTI data involving the same CC areas correlated instead with Aβ42-stimulated interleukin (IL)-21 producing CD4+ T lymphocytes. Higher susceptibility to PDL-1-mediated apoptosis of Aβ42-specific lymphocytes and BDNF-associated survival of existing neurons could contribute to the relative CC structure preservation seen in aMCI. These potentially protective mechanisms are lost in frank AD, when severe alterations in the CC are mirrored in peripheral blood by proinflammatory cytokines-producing T cells. Monitoring of immune cells in peripheral blood could have a prognostic value in AD.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disorder involving both gray matter (GM) and white matter (WM) tissues that is well defined as a part of a continuum of clinical and biological phenomena
DTI ANALYSES Significantly reduced fractional anisotropy (FA) values were found in the frontal corpus callosum (CC) regions (CC2–CC3) of AD compared to amnestic mild cognitive impairment (aMCI) subjects (p < 0.01)
PD-1-expressing CD4+ and CD8+ T lymphocytes and PD-L1-expressing CD14+ and CD19+ cells in Aβ42-peptide-stimulated PBMC PD-1 on T lymphocytes binds PD-L1 on the surface of antigen presenting cells (APC) resulting in the dampening of adaptive immune-response via tolerization or apoptosis of antigenspecific T lymphocytes
Summary
Alzheimer’s disease (AD) is a neurodegenerative disorder involving both gray matter (GM) and white matter (WM) tissues that is well defined as a part of a continuum of clinical and biological phenomena. Recent results indicated that a significant reduction of PD-1- and PDL1-expressing cells is present in AD and amnestic mild cognitive impairment (aMCI), a prodromal stage of AD. The interaction between these molecules is responsible for the induction of tolerance and for the apoptosis of antigen-specific cells (Francisco et al, 2010); as the impairment seen in AD and aMCI is specific for Aβ-stimulated cells, this alteration could play a role in the neuroinflammation accompanying AD (Saresella et al, 2012)
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