RESUMEN
Several studies have revealed defects in autophagy in neurodegenerative disorders including Alzheimer's disease (AD) and frontotemporal dementia (FTD). SQSTM1/p62 plays a key role in the autophagic machinery and may serve as a marker for autophagic flux in vivo. We investigated the role of p62 in neurodegeneration, analyzing its concentrations in the CSF of AD and FTD patients. We recruited 76 participants: 22 patients with AD, 28 patients with FTD, and 26 controls. CSF p62 concentrations were significantly increased in AD and FTD patients when compared to controls, which persisted after adjusting for age (p = 0.01 and p = 0.008, respectively). In female FTD patients, p62 positively correlated with the neurodegenerative biomarkers t-Tau and p-Tau. A significant correlation between CSF p62 concentrations and several clinical features of AD was found. Our data show that p62 is increased in CSF of AD and FTD patients, suggesting a key role of autophagy in these two disorders. The levels of p62 in CSF may reflect an altered autophagic flux, and p62 could represent a potential biomarker of neurodegeneration.
RESUMEN
BACKGROUND: An autoimmune hypothesis has been suggested for a subtype of Obsessive-Compulsive Disorder (OCD) with childhood onset: obsessions, compulsions and/or tics would result from anti-streptococcal antibodies that cross-react with basal ganglia tissue based on molecular mimicry. Consistent with this hypothesis anti-brain antibodies were detected in sera of children with OCD and/or Tourette's syndrome. In the present study, we tested whether adults with OCD have anti-brain antibodies or other antibodies that serve as markers of autoimmunity. METHODS: Seventy-four DSM-IV OCD (YBOCS> or =16) subjects were recruited and compared to 44 controls with a current Major Depressive Episode for neurological symptoms, ALSO titres, anti-tissue and anti-thyroid antibodies. Anti-brain antibodies were tested by immunohistochemistry and Western blotting methods. RESULTS: The proportion of subjects with tic comorbidity or positive ASLO titre (>200 IU/ml) was significantly greater in OCD than in MDE patients (21.6 vs. 2.3% and 16.3 vs. 2.3%, respectively). No other differences in antibody parameters were found. 4/74 OCD patients (5.4%) and none of the controls resulted positive for anti-brain antibodies, with a band around 50-60 kDa at the Western blot analysis. LIMITATIONS: The methodology used to assess anti-brain antibodies. CONCLUSIONS: The majority of adult OCD patients do not seem to have autoimmunity disturbances as compared to a control group. However, a greater percentage of subjects with positive ASLO titres were found among OCD patients. For a small proportion of OCD patients, moreover, autoimmune reactions towards neuronal structures are present although further investigations are needed to demonstrate its etiopathogenetic relevance.