Optimizing filter trap assay for the detection of aggregated alpha-synuclein in brain samples

No abstract availabl

Tau expression and phosphorylation in enteroendocrine cells

Background and objectiveThere is mounting evidence to suggest that the gut-brain axis is involved in the development of Parkinson’s disease (PD). In this regard, the enteroendocrine cells (EEC), which faces the gut lumen and are connected with both enteric neurons and glial cells have received growing attention. The recent observation showing that these cells express alpha-synuclein, a presynaptic neuronal protein genetically and neuropathologically linked to PD came to reinforce the assumption that EEC might be a key component of the neural circuit between the gut lumen and the brain for the bottom-up propagation of PD pathology. Besides alpha-synuclein, tau is another key protein involved in neurodegeneration and converging evidences indicate that there is an interplay between these two proteins at both molecular and pathological levels. There are no existing studies on tau in EEC and therefore we set out to examine the isoform profile and phosphorylation state of tau in these cells.MethodsSurgical specimens of human colon from control subjects were analyzed by immunohistochemistry using a panel of anti-tau antibodies together with chromogranin A and Glucagon-like peptide-1 (two EEC markers) antibodies. To investigate tau expression further, two EEC lines, namely GLUTag and NCI-H716 were analyzed by Western blot with pan-tau and tau isoform specific antibodies and by RT-PCR. Lambda phosphatase treatment was used to study tau phosphorylation in both cell lines. Eventually, GLUTag were treated with propionate and butyrate, two short chain fatty acids known to sense EEC, and analyzed at different time points by Western blot with an antibody specific for tau phosphorylated at Thr205.ResultsWe found that tau is expressed and phosphorylated in EEC in adult human colon and that both EEC lines mainly express two tau isoforms that are phosphorylated under basal condition. Both propionate and butyrate regulated tau phosphorylation state by decreasing its phosphorylation at Thr205.Conclusion and inferenceOur study is the first to characterize tau in human EEC and in EEC lines. As a whole, our findings provide a basis to unravel the functions of tau in EEC and to further investigate the possibility of pathological changes in tauopathies and synucleinopathies

Pupil size as an indicator of cognitive activity in mild Alzheimer's Disease

International audienceIt is well established that pupil activity indexes cognitive processing. For instance, research has consistently demonstrated that the pupil reacts to working memory span task performance. However, little is known about pupil reaction to cognitive processing in Alzheimer’s Disease (AD). We thus investigated whether span tasks can modulate pupil size in patients with AD. We invited 24 patients with AD and 24 healthy older adults to perform backward and forward spans, as well as to count aloud in a control condition, while their pupil activity was recorded with an eye tracking glasses. In patients with AD, analysis demonstrated larger pupil size during backward spans (M = 2.12, SD = .39) than during forward spans (M = 1.98, SD = .36)[t(23) = 3.22, p = .004], larger pupil size during forward spans than during counting (M = 1.67, SD = .33) [t(23) = 4.75, p < .001], as well as larger pupil size during backward spans than during counting [t(23) = 10.60, p < .001]. In control participants, analysis demonstrated larger pupil size during backward spans (M = 3.36, SD = .49) than during forward spans (M = 2.85, SD = .68) [t(23) = 5.82, p < .001], larger pupil size during forward spans than during counting (M = 2.09, SD = .62) [t(23) = 5.42, < .001], as well as larger pupil size during backward spans than during counting [t(23) = 9.70, p < .001]. Results also demonstrated a significant interaction effect between groups and conditions [F(2,92) = 16.63, p < .001]; in other words, patients with AD have showed fewer variations on the pupil size across the conditions compared to the control participants. The larger pupil size during backward spans, compared with forward spans or counting, can be attributed to the high cognitive load of backward spans. The modulation of pupil size, as observed across backward/forward spans and counting, can possibly be attributed to sympathetic/adrenergic and parasympathetic/cholinergic activities. Our study demonstrates the value of pupillometry as a potential biomarker of cognitive processing in AD

Pupil size as an indicator of cognitive activity in mild Alzheimer's Disease

International audienceIt is well established that pupil activity indexes cognitive processing. For instance, research has consistently demonstrated that the pupil reacts to working memory span task performance. However, little is known about pupil reaction to cognitive processing in Alzheimer’s Disease (AD). We thus investigated whether span tasks can modulate pupil size in patients with AD. We invited 24 patients with AD and 24 healthy older adults to perform backward and forward spans, as well as to count aloud in a control condition, while their pupil activity was recorded with an eye tracking glasses. In patients with AD, analysis demonstrated larger pupil size during backward spans (M = 2.12, SD = .39) than during forward spans (M = 1.98, SD = .36)[t(23) = 3.22, p = .004], larger pupil size during forward spans than during counting (M = 1.67, SD = .33) [t(23) = 4.75, p < .001], as well as larger pupil size during backward spans than during counting [t(23) = 10.60, p < .001]. In control participants, analysis demonstrated larger pupil size during backward spans (M = 3.36, SD = .49) than during forward spans (M = 2.85, SD = .68) [t(23) = 5.82, p < .001], larger pupil size during forward spans than during counting (M = 2.09, SD = .62) [t(23) = 5.42, < .001], as well as larger pupil size during backward spans than during counting [t(23) = 9.70, p < .001]. Results also demonstrated a significant interaction effect between groups and conditions [F(2,92) = 16.63, p < .001]; in other words, patients with AD have showed fewer variations on the pupil size across the conditions compared to the control participants. The larger pupil size during backward spans, compared with forward spans or counting, can be attributed to the high cognitive load of backward spans. The modulation of pupil size, as observed across backward/forward spans and counting, can possibly be attributed to sympathetic/adrenergic and parasympathetic/cholinergic activities. Our study demonstrates the value of pupillometry as a potential biomarker of cognitive processing in AD

Tau in the gut, does it really matter?

International audienc

“Who will I be?”: The future of the self as described by Alzheimer's disease (AD) patients

International audienceWe assessed how Alzheimer’s disease (AD) patients would imagine their self in the future. AD patients andhealthy controls were asked to generate statements beginning with “I-will-be” to describe how they sawthemselves or how they wished to be in the future. These statements were analyzed in terms of four self-dimensions, i.e., physical self, social self, psychological self and self-cessation. The latter was investigated toassess how AD patients processed the idea of their own mortality. Findings demonstrated fewer total “I-will-be” statements in AD participants than in controls, suggesting that the construction of future self-conceptsbecomes weaker in the disease. Our results also demonstrated fewer statements related to the physical-self,the social-self and the psychological-self, and more statements related to self-cessation in AD participantsthan in controls. These findings suggest that AD patients are highly preoccupied by the idea of death whenthinking about the future of their self

Multimorbidities and Overprescription of Proton Pump Inhibitors in Older Patients.

To determine whether there is an association between overprescription of proton pump inhibitors (PPIs) and multimorbidities in older patients.Multicenter prospective study.Acute geriatric medicine at the University Hospital of Nantes and the Hospital of Saint-Nazaire.Older patients aged 75 and over hospitalized in acute geriatric medicine.Older patients in acute geriatric medicine who received proton pump inhibitors. Variables studied were individual multimorbidities, the burden of multimorbidity evaluated by the Cumulative Illness Rating Scale, age, sex, type of residence (living in nursing home or not), functional abilities (Lawton and Katz scales), nutritional status (Body Mass Index), and the type of concomitant medications (antiaggregant, corticosteroids', or anticoagulants).Overprescription of proton pump inhibitors was found in 73.9% older patients. In the full model, cardiac diseases (odds ratio [OR] = 4.17, p = 0.010), metabolic diseases (OR = 2.14, p = 0.042) and corticosteroids (OR = 5.39, p = 0.028) were significantly associated with overprescription of proton pump inhibitors. Esogastric diseases (OR = 0.49, p = 0.033) were negatively associated with overprescription of proton pump inhibitors.Cardiac diseases and metabolic diseases were significantly associated with overprescription of proton pump inhibitors