<i>Background:</i> Neurofibrillary tangles and senile plaques are hallmarks of Alzheimer’s disease (AD) although the molecular basis of their coexistence remains elusive. The peptidyl-prolyl <i>cis/trans</i> isomerase Pin1 acts on both tau and amyloid precursor protein to regulate their functions by influencing tau phosphorylation and amyloid precursor protein processing. <i>Objective:</i> In order to identify potential biomarkers for AD in easily accessible cells and to gain insight into the relationship between the brain and peripheral compartments in AD pathology, we investigated Pin1 expression and activity in the peripheral blood mononuclear cells of subjects with late-onset AD (LOAD) and age-matched controls (CT). <i>Methods:</i> Gene and protein expression, promoter methylation, Ser<sup>16</sup> phosphorylation and activity of Pin1 were evaluated in 32 samples from subjects with LOAD and in 28 samples from CT. <i>Results:</i> In LOAD subjects, there was a statistically significant reduction in Ser<sup>16</sup> phosphorylation (–30%; p = 0.041) and promoter methylation (–8%; p = 0.001), whereas Pin1 expression was significantly increased (+74%; p = 0.018). <i>Conclusion:</i> The modifications of Pin1 found in LOAD subjects support its involvement in the pathogenesis of the disease with an important role being played by epigenetic mechanisms.
"We are all in this together" - we often hear this phrase when we want to flag up a problem that is not for a single individual but concerns us all. A similar reflection has been recently made in the field of mental disorders where brain-centric scientists have started to zoom out their brain-focused graphical representations of the mechanisms regulating psychiatric diseases to include other organs or mediators that did not belong historically to the world of neuroscience. The brain itself - that has long been seen as a master in command secluded in its fortress (the blood brain barrier), has now become a collection of Airbnb(s) where all sorts of cells come in and out and sometimes even rearrange the furniture! Under this new framework of reference, mental disorders have become multisystem pathologies where different biological systems - not just the CNS -contribute 'all together' to the development and severity of the disease. In this narrative review article, we will focus on one of the most popular biological systems that has been shown to influence the functioning of the CNS: the immune system. We will specifically highlight the two main features of the immune system and the CNS that we think are important in the context of mental disorders: plasticity and memory.
