Objective: We have assessed whether tau and amyloid beta deposits might be present in pancreatic tissue of subjects with Parkinson’s and Lewy Body dementia.

Background: Synucleinopathies are complex neurodegenerative disorders with a broad spectrum of motor and nonmotor features. Among these factors, a handful of epidemiological studies have highlighted that pre-existing type 2 diabetes mellitus (T2DM) may be a risk factor for developing Parkinson’s disease (PD). We have previously published that 93% of PD patients have cytoplasmic alpha-synuclein deposits in pancreatic beta-cells. Furthermore, we found the same inclusions in 68% of neurologically asymptomatic subjects with T2DM, and in 17% of control subjects. But besides alpha-synuclein, in the brain of PD patients are also present deposits of pathological protein aggregates, like tau and beta-amyloid are also found in the brain of Parkinson’s disease and Lewy Body dementia.

Method: We studied pancreatic and brain tissue from 39 individuals with no neuropathological alterations, and from 39 subjects diagnosed with Parkinson’s disease and Lewy Body dementia. We examined amyloid-beta and tau (ten different subtypes) accumulation in the pancreas. Moreover, we performed proximity ligation assays to assess whether tau and/or amyloid-beta interact with amylin and synuclein in the pancreas.

Results: Cytoplasmic tau and amyloid-beta protein deposits were detected in pancreatic beta-cells of subjects with Parkinson’s disease, as well as in subjects with a normal neuropathological profile but with a history of T2DM and in a small cohort of control subjects without T2DM. Furthermore, we provide the first histological evidence that either alpha-synuclein and amylin can interact with amyloid-beta and tau in the pancreas.

Conclusion: The presence of both tau and amyloid-beta inclusions in pancreatic beta-cells, provides new evidence of a potential overlap in the mechanisms underlying the pathogenesis of T2DM, Parkinson’s disease and Alzheimer’s disease. Moreover, the interaction of amylin with tau and amyloid-beta in pancreatic beta-cells, may represent a novel target to develop therapies for these diseases.

« Back to 2019 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/tau-and-amyloid-beta-inclusions-are-present-in-pancreatic-beta-cells-of-patients-with-synucleinopathies/