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Article type: Research Article
Authors: Tilley, Bension S.; * | Patel, Shivani R. | Goldfinger, Marc H. | Pearce, Ronald K.B. | Gentleman, Steve M.
Affiliations: Neuropathology Unit, Department of Brain Sciences, Imperial College London, London, UK
Correspondence: [*] Correspondence to: Bension S. Tilley, Neuropathology Unit, Department of Brain Sciences, 4/F Burlington Danes Building, Hammersmith Campus, Imperial College London, London W12 0NN, UK. Tel.: +44 7806506522; E-mail: [email protected].
Abstract: Background:Lewy body dementia (LBD) has two main phenotypes: Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB), separated by the ‘one-year-rule’. They also show different symptom profiles: core DLB features include fluctuating cognition, REM-sleep behaviur disorder, and visual hallucinations. These symptoms are sometimes present in PDD, representing an intermediate ‘PDD-DLB’ phenotype. Objective:DLB-like features may reflect deficits in the functions of the noradrenergic nucleus locus coeruleus (LC). Therefore, we compared the LC in the LBD phenotypes, PD, and controls. Methods:38 PD, 56 PDD, 22 DLB, and 11 age-matched control cases from the Parkinson’s UK tissue bank were included. LC tissue sections were immunostained for tyrosine-hydroxylase (TH), α-synuclein, tau, and amyloid-β. TH-neurons were quantified and pathologic burden calculated by %-coverage method. Results:The LC shows a stepwise reduction in neuron count from controls, PD, PDD, to DLB. PDD-DLB cases showed an intermediate clinical phenotype that was reflected pathologically. Cell counts were significantly reduced in DLB compared to PDD after correction for demographic factors. LC degeneration contributed significantly to the onset of all DLB symptoms. While α-synuclein was not significantly different between PDD and DLB cases, DLB exhibited significantly less tau pathology. Conclusion:DLB and DLB-like symptoms represent noradrenergic deficits resulting from neuronal loss in the LC. PDD and DLB are likely to represent a clinical continuum based on the presence or absence of DLB-like symptoms mirrored by a pathological continuum in the LC.
Keywords: Alpha-synuclein, Lewy body disease, locus coeruleus, neuropathology, Parkinson’s disease, tau proteins
DOI: 10.3233/JPD-212748
Journal: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1641-1650, 2021
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