Accumulation of amyloid-β in the cerebellar cortex of essential tremor patients

The accumulation of insoluble amyloid-beta (A beta) peptides is associated with neurodegenerative disorders, such as Alzheimer's disease (AD). As essential tremor (ET) could involve neurodegenerative processes in the cerebellum, we quantified soluble and insoluble A beta in cerebellar cortices from patients diagnosed with ET (n = 9), compared to Controls (n = 16) or individuals with Parkinson's disease (n = 10). Although ante-mortem cognitive performance was not documented, all individuals included had the diagnosis of AD ruled out by a neuropathologist ELISA-determined concentrations of insoluble A beta 42 in ET patients displayed a bimodal distribution, with a median 246-fold higher than in Controls (P < 0.01, Kruskal-Wallis). Higher A beta 42 concentrations were measured in the parietal cortex of the same ET patients, compared to Controls (107-fold median increase, P < 0.01, Kruskal-Wallis), but similar phosphorylated tau levels were detected. The rise in cerebellar insoluble A beta 42 concentrations is not associated to APP expression and processing or the ApoE4 status. However, A beta 42 levels in ET individuals were correlated with cerebellar insoluble phosphorylated tau (r(2) = 0.71, P = 0.005), unphosphorylated neurofilament heavy chain (NF-H; r(2) = 0.50, P = 0.030) and Lingo-1 (r(2) = 0.73, P = 0.007), indicative of a generalized neurodegenerative process involving the cerebellum. Our results suggest prevalent accumulations of insoluble A beta 42 in the cerebellum of ET, but not in age-matched PD. Whether this anomaly plays a role in ET symptoms warrants further investigations. (C) 2015 Elsevier Inc. All rights reserved.