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Neurobiol Dis. 2015 Oct;82:397-408. doi: 10.1016/j.nbd.2015.07.016. Epub 2015 Aug 5.

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

Author information

1
Faculty of Pharmacy, Université Laval, Québec, QC, Canada; Neurosciences Axis, Centre de recherche du CHU de Québec, Québec, QC, Canada.
2
Faculty of Pharmacy, Université Laval, Québec, QC, Canada.
3
Division of Neurology, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada.
4
Faculty of Pharmacy, Université Laval, Québec, QC, Canada; Neurosciences Axis, Centre de recherche du CHU de Québec, Québec, QC, Canada. Electronic address: frederic.calon@crchul.ulaval.ca.

Abstract

The accumulation of insoluble amyloid-beta (Aβ) 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 Aβ 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 Aβ42 in ET patients displayed a bimodal distribution, with a median 246-fold higher than in Controls (P<0.01, Kruskal-Wallis). Higher Aβ42 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 Aβ42 concentrations is not associated to APP expression and processing or the ApoE4 status. However, Aβ42 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 Aβ42 in the cerebellum of ET, but not in age-matched PD. Whether this anomaly plays a role in ET symptoms warrants further investigations.

KEYWORDS:

Amyloid beta; Cerebellum; Essential tremor

PMID:
26253607
DOI:
10.1016/j.nbd.2015.07.016
[Indexed for MEDLINE]

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