Objective: We studied whether, as in the brain, pancreatic -cells of subjects with neurodegenerative diseases also present co-occurrence of other misfolded proteins. Furthermore, we also assessed the pancreatic expression of PrP, in subjects with Alzheimer’s disease (AD), Parkinson’s disease (PD) and control subjects and its interaction, both in the pancreas and brain, with alpha-synuclein, tau, beta-amyloid and amylin.

Background: Although protein misfolding diseases exhibits characteristic protein inclusions, several lines of evidence have shown that co-occurrence of other misfolded proteins, related either with other neurodegenerative or non-degenerative (vascular or metabolic) conditions is a frequent event in the brains of these patients. Understanding the impact of these concomitant proteins has an outstanding relevance, as it may help to unravel the considerable differences in clinical presentations of what were previously considered homogenous neurodegenerative entities.

Method: Pancreatic tissues from 138 autopsies were evaluated in this retrospective study. We examined amyloid-beta and tau (ten different subtypes) accumulation in PD subjects and alpha-synuclein deposition in EA subjects. Moreover, we performed proximity ligation assays to assess whether PrP interacts other amyloidogenic proteins

Results: The main findings of our work are:
Amylin, alpha-synuclein, tau, and PrP immunoreactivity is increased in pancreatic cells of subjects with neurodegenerative diseases or with T2DM.
alfa-synuclein aggregates are present in pancreatic beta-cells of subjects with AD.
Tau and Abeta deposits are found in pancreatic beta-cells of subjects with synucleinopathies.
PrP is primarily expressed in pancreatic beta-cells and binds to amylin, alfa-synuclein, tau and Abeta either in the pancreas and in the locus coeruleus

Conclusion: The presence of both tau and amyloid-beta inclusions in pancreatic beta-cells of PD patients, and of alpha-synuclein in pancreatic beta-cells of EA patients provides new evidence of a potential overlap in the mechanisms underlying the pathogenesis of PD and AD. Moreover, the interaction of PrP with amylin, tau amyloid-beta and synuclein may represent a novel target to develop therapies for these diseases.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/mixed-pathologies-in-pancreatic-beta-cells-from-subjects-with-neurodegenerative-diseases-and-their-interaction-with-prion-protein/