Concomitant pathologies among a spectrum of parkinsonian disorders

Dugger, Brittany N.; Adler, Charles H.; Shill, Holly A.; Caviness, John N.; Jacobson, Sandra A.; Driver‐Dunckley, Erika; Beach, Thomas G.

doi:10.1016/j.parkreldis.2014.02.012

Cited by 114 publications

(99 citation statements)

References 39 publications

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“…These results would suggest that in human brains, LB structures consisting of abnormal aggregates of phosphorylated α-synuclein do not have the same inflammation-inducing effects compared to AD pathological structures. The presence of mixed pathologies is a feature of most postmortem brains from subjects with neurodegenerative diseases and needs to be considered in human focused studies (Dugger et al, 2012, 2014)…”

Section: Discussionmentioning

confidence: 99%

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Changes in CD200 and intercellular adhesion molecule-1 (ICAM-1) levels in brains of Lewy body disorder cases are associated with amounts of Alzheimer's pathology not α-synuclein pathology

Walker

Lue

Tang

et al. 2017

Neurobiology of Aging

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Enhanced inflammation has been associated with Alzheimer’s disease (AD) and diseases with Lewy body (LB) pathology, such as Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB). One issue is whether amyloid and tangle pathology, features of AD, or α-synuclein LB pathology have similar or different effects on brain inflammation. An aim of this study was to examine if certain features of inflammation changed in brains with increasing LB pathology. To assess this, we measured levels of the anti-inflammatory protein CD200 and the pro-inflammatory protein intercellular adhesion molecule-1 (ICAM-1) in cingulate and temporal cortex from a total of 143 cases classified according to the Unified Staging System for LB disorders. Changes in CD200 and ICAM-1 levels did not correlate with LB pathology, but with AD pathology. CD200 negatively correlated with density of neurofibrillary tangles, phosphorylated tau and amyloid plaque density. ICAM-1 positively correlated with these AD pathology measures. Double immunohistochemistry for phosphorylated α-synuclein and markers for microglia showed limited association of microglia with LB pathology, but microglia strongly associated with amyloid plaques or phosphorylated tau. These results suggest that there are different features of inflammatory pathology in diseases associated with abnormal α-synuclein compared to AD.

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Section: Discussionmentioning

confidence: 99%

“…These studies also observed a significant role for the amount of concurrent AD pathology in determining the degree of microglial activation in these LB diseases. The presence of coexisting AD is a common feature in LB disease affected brains (Dugger et al, 2014) .…”

Section: Introductionmentioning

confidence: 99%

Changes in CD200 and intercellular adhesion molecule-1 (ICAM-1) levels in brains of Lewy body disorder cases are associated with amounts of Alzheimer's pathology not α-synuclein pathology

Walker

Lue

Tang

et al. 2017

Neurobiology of Aging

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“…36 In a recent study, a higher sleep fragmentation was associated with a higher number of postmortem identified macroscopic infarcts and more severe atherosclerosis. 37 However, it remains unknown whether amyloid angiopathy has a role in RBD pathogenesis.…”

Section: Insomniamentioning

confidence: 93%

Probable REM sleep behavior disorder and risk of stroke

Pavlova

Liu

et al. 2017

Neurology

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Objective: To examine whether probable REM sleep behavior disorder (pRBD) was associated with increased risk of developing stroke in a community-based cohort. Methods:The study included 12,003 participants (mean age 54.0 years) of the Kailuan Study, free of stroke, cancer, Parkinson disease, dementia, and head injury at baseline (2012). We determined pRBD using a validated REM sleep behavior disorder (RBD) questionnaire in 2012. Incident stroke cases were confirmed by review of medical records. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of stroke according to pRBD status, adjusting for several sleep measures (i.e., insomnia, daytime sleepiness, sleep duration, snoring, and use of hypnotics) and other potential confounders.Results: During 3 years of follow-up, we documented 159 incident stroke cases. Relative to participants without pRBD at the baseline, those with pRBD had a 157% higher risk (95% CI 59%-313%) of developing stroke. Presence of pRBD was associated with increased risk of both stroke types-the adjusted HR was 1.93 (95% CI 1.07-3.46) for ischemic stroke and 6.61 (95% CI 2.27-19.27) for hemorrhagic stroke.Conclusions: Presence of pRBD was associated with a higher risk of developing stroke, including both ischemic and hemorrhagic types. Future studies with clinically confirmed RBD and a longer follow-up would be appropriate to further investigate this association. Neurology ® 2017;88:1849-1855 GLOSSARY AIS 5 Athens Insomnia Scale; BMI 5 body mass index; CI 5 confidence interval; ESS 5 Epworth Sleepiness Scale; HDL-C 5 high-density lipoprotein cholesterol; HR 5 hazard ratio; ICD-10 5 International Classification of Diseases-10; LDL-C 5 lowdensity lipoprotein cholesterol; OR 5 odds ratio; OSA 5 obstructive sleep apnea; PD 5 Parkinson disease; pRBD 5 probable REM sleep behavior disorder; RBD 5 REM sleep behavior disorder; RBDQ-HK 5 RBD questionnaire-Hong Kong; RMB 5 renminbi.REM sleep behavior disorder (RBD) is associated with synucleinopathies, and a large proportion of individuals with RBD may already have or later develop Parkinson disease (PD), dementia with Lewy bodies, or multiple system atrophy. [1][2][3] Synucleinopathies were often associated with symptoms of autonomic dysfunction, such as impaired blood pressure control and reduced heart rate variability. 4,5 Consistently, individuals with idiopathic RBD experienced worse autonomic function, including cardiovascular, gastrointestinal, and urinary domains, relative to control participants. 6,7 The autonomic nervous system may have a role in the prepathologic state or contribute to the precipitating factors of the acute phase of stroke, such as atherosclerosis and sympathetic hyperactivity. 8 Some case reports suggested that stroke may cause RBD. 9-11 In a previous cross-sectional study, we also found that individuals with probable RBD (pRBD) had higher odds of several concurrent stroke risk factors, such as diabetes and hyperlipidemia. 12 However, whether RBD predicts subsequ...

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“…In a recent study evaluating 64 cases of pathologically proven PSP, 36% had concomitant AD, 20% PD, 1% DLB, 44% argyrophilic grains, 52% cerebral white matter rarefaction and 25% cerebral amyloid angiography. 30 …”

Section: Symptomatic Psp Phenotypesmentioning

confidence: 99%

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

Boxer

Golbe

et al. 2017

The Lancet Neurology

332

359

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Progressive supranuclear palsy (PSP), once simply considered a common cause of atypical parkinsonism is now recognized as a spectrum of motor and behavioral syndromes associated with a specific four repeat (4R) tau neuropathology at autopsy. There are currently no effective treatments for PSP, but because PSP is strongly linked biochemically and genetically to tau protein abnormalities, there is a growing interest in pursuing clinical trials of new tau-directed therapies for this disorder. Such new tau therapies are envisioned to have disease-modifying effects by reducing brain levels of toxic forms of tau or compensating for loss of tau function. To be most effective, these treatments will need to be initiated at early stages of disease. New research criteria that recognize early forms of PSP and operationalize diagnosis of the full spectrum of clinical phenotypes have recently been published. These criteria and new clinical trial designs have benefited from rapid advances in MRI, physiological and fluid biomarker development for PSP. As tau pathology is also central to Alzheimer’s disease and chronic traumatic encephalopathy, it is believed that a successful tau therapeutic for PSP would inform the treatment of other neurodegenerative diseases.

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Concomitant pathologies among a spectrum of parkinsonian disorders

Cited by 114 publications

References 39 publications

Changes in CD200 and intercellular adhesion molecule-1 (ICAM-1) levels in brains of Lewy body disorder cases are associated with amounts of Alzheimer's pathology not α-synuclein pathology

Changes in CD200 and intercellular adhesion molecule-1 (ICAM-1) levels in brains of Lewy body disorder cases are associated with amounts of Alzheimer's pathology not α-synuclein pathology

Probable REM sleep behavior disorder and risk of stroke

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

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