Journal
NEUROBIOLOGY OF DISEASE
Volume 82, Issue -, Pages 397-408Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2015.07.016
Keywords
Essential tremor; Cerebellum; Amyloid beta
Categories
Funding
- Association des personnes concernees par le tremblement essentiel (Aptes)
- International Essential Tremor Foundation (IETF)
- Canada Foundation for Innovation [10307]
- Fonds de la recherche en sante du Quebec [26936]
- Parkinson Curling Classic
- Greystone Golf Classic
- Royal University Hospital Foundation
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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.
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