title: Accumulation of amyloid-β in the cerebellar cortex of essential tremor patients.
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.
authors.affiliation: Faculty of Pharmacy, Université Laval, Québec, QC, Canada; Neurosciences Axis, Centre de recherche du CHU de Québec, Québec, QC, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Béliveau
authors.affiliation: Faculty of Pharmacy, Université Laval, Québec, QC, Canada; Neurosciences Axis, Centre de recherche du CHU de Québec, Québec, QC, Canada.
authors.forename: Cyntia
authors.initials: C
authors.lastname: Tremblay
authors.affiliation: Faculty of Pharmacy, Université Laval, Québec, QC, Canada; Neurosciences Axis, Centre de recherche du CHU de Québec, Québec, QC, Canada.
authors.forename: Émilie
authors.initials: É
authors.lastname: Aubry-Lafontaine
authors.affiliation: Faculty of Pharmacy, Université Laval, Québec, QC, Canada; Neurosciences Axis, Centre de recherche du CHU de Québec, Québec, QC, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Paris-Robidas
authors.affiliation: Faculty of Pharmacy, Université Laval, Québec, QC, Canada.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Delay
authors.affiliation: Division of Neurology, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Robinson
authors.affiliation: Division of Neurology, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Les
authors.initials: L
authors.lastname: Ferguson
authors.affiliation: Division of Neurology, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Rajput
authors.affiliation: Division of Neurology, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Rajput
authors.affiliation: 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.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Calon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000378:metabolism; D002525:Cerebellar Cortex / Q000378:metabolism*; D020329:Essential Tremor / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D010296:Parietal Lobe / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation; D011689:Purkinje Cells / Q000378:metabolism; D013702:Temporal Lobe / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; C482293:LINGO1 protein, human; C054369:MAPT protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins; C051774:neurofilament protein H
keywords: Amyloid beta; Cerebellum; Essential tremor