Various neurodegenerative disorders have been associated with an inappropriate reaction to dietary gluten intake. The underlying neuropathological mechanism is still unclear. We postulated that the inflicted neuronal damage is immune-mediated, like in the intestine. In this project we will further investigate the humoral and t-cell mediated response in these patients.

This project consists of three studies. We postulated that lymphocytic infiltration leads to  neuronal damage, especially to Purkinje cells in the cerebellum. Post-mortem cerebellar tissue was collected of patients with coeliac disease that died of an idiopathic, neurodegenerative disease. Gender- and age-matched genetic ataxia (SCA) controls and non-neurological controls (NNC) were selected based on clinical reports and pathological findings. FFPE cerebellar sections were stained for CD3, CD8, CD20, Iba-1, Granzyme B, CD68 and Calbindin and microglial activity was measured. Our aim was to determine the loss of neurons, especially Purkinje cells, and the location of both innate and adaptive immune cells in the cerebellum of patients with CD and a concomitant idiopathic neurological disease affecting the cerebellum.

We also hypothesized that patients with a gluten-related neurological disorder produce gluten-related antibodies. In collaboration with Radboudumc, Universitair Medisch Centrum Utrecht, Maastricht UMC+ we gathered large cohorts of patients with idiopathic neuropathy or ataxia and gender- and age-matched controls. Serum samples were analyzed for anti-Transglutaminase 2, anti-Transglutaminase 6 and anti-gliadin antibodies. The last project is a prospective cohort study; we will study the effect of a gluten-free diet on symptoms and MR-spectroscopy of the cerebellum in patients with idiopathic ataxia and gluten sensitivity.

These projects will tell us if there is a specific immune response in gluten-related neurological disorders, whether gluten-related antibodies might function as a marker and if a gluten-free diet might be an effective intervention.

Amsterdam UMC researchers involved in this project: