Locus coeruleus pathology in progressive supranuclear palsy, and its relation to disease severity.

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ID: 91656
2020
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Ranked #8 of 95 articles by views in acta neuropathologica communications

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Abstract
The locus coeruleus is the major source of noradrenaline to the brain and contributes to a wide range of physiological and cognitive functions including arousal, attention, autonomic control, and adaptive behaviour. Neurodegeneration and pathological aggregation of tau protein in the locus coeruleus are early features of progressive supranuclear palsy (PSP). This pathology is proposed to contribute to the clinical expression of disease, including the PSP Richardson's syndrome. We test the hypothesis that tau pathology and neuronal loss are associated with clinical heterogeneity and severity in PSP.We used immunohistochemistry in post mortem tissues from 31 patients with a clinical diagnosis of PSP (22 with Richardson's syndrome) and 6 control cases. We quantified the presence of hyperphosphorylated tau, the number of pigmented cells indicative of noradrenergic neurons, and the percentage of pigmented neurons with tau-positive inclusions. Ante mortem assessment of clinical severity using the PSP rating scale was available within 1.8 (±0.9) years for 23 patients.We found an average 49% reduction of pigmented neurons in PSP patients relative to controls. The loss of pigmented neurons correlated with disease severity, even after adjusting for disease duration and the interval between clinical assessment and death. The degree of neuronal loss was negatively associated with tau-positive inclusions, with an average of 44% of pigmented neurons displaying tau-inclusions.Degeneration and tau pathology in the locus coeruleus are related to clinical heterogeneity of PSP. The noradrenergic deficit in the locus coeruleus is a candidate target for pharmacological treatment. Recent developments in ultra-high field magnetic resonance imaging to quantify in vivo structural integrity of the locus coeruleus may provide biomarkers for noradrenergic experimental medicines studies in PSP.
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kaalund2020locusacta Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Kaalund, Sanne Simone;Passamonti, Luca;Allinson, Kieren S J;Murley, Alexander G;Robbins, Trevor W;Spillantini, Maria Grazia;Rowe, James B;
Journal acta neuropathologica communications
Year 2020
DOI
10.1186/s40478-020-0886-0
URL
Keywords
tau neurodegeneration frontotemporal dementia locus coeruleus noradrenalin progressive supranuclear palsy

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