Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC

Abstract The diagnosis and treatment of synucleinopathies such as Parkinson disease and dementia with Lewy bodies would be aided by the availability of assays for the pathogenic disease-associated forms of α-synuclein (αSynD) that are sufficiently sensitive, specific, and practical for analysis of accessible diagnostic specimens. Two recent αSynD seed amplification tests have provided the first prototypes for ultrasensitive and specific detection of αSynD in patients’ cerebrospinal fluid. These prototypic assays require 5–13 days to perform. Here, we describe an improved α-synuclein real time quaking-induced conversion (αSyn RT-QuIC) assay that has similar sensitivity and specificity to the prior assays, but can be performed in 1–2 days with quantitation. Blinded analysis of cerebrospinal fluid from 29 synucleinopathy cases [12 Parkinson’s and 17 dementia with Lewy bodies] and 31 non-synucleinopathy controls, including 16 Alzheimer’s cases, yielded 93% diagnostic sensitivity and 100% specificity for this test so far. End-point dilution analyses allowed quantitation of relative amounts of αSynD seeding activity in cerebrospinal fluid samples, and detection in as little as 0.2 μL. These results confirm that αSynD seeding activity is present in cerebrospinal fluid. We also demonstrate that it can be rapidly detected, and quantitated, even in early symptomatic stages of synucleinopathy.

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Alpha-synuclein in the Cerebrospinal Fluid Differentiates Synucleinopathies (Parkinson Disease, Dementia With Lewy Bodies, Multiple System Atrophy) From Alzheimer Disease

Alzheimer Disease & Associated Disorders ◽

10.1097/wad.0b013e31823899cc ◽

2012 ◽

Vol 26 (3) ◽

pp. 213-216 ◽

Cited By ~ 77

Author(s):

Fuyuki Tateno ◽

Ryuji Sakakibara ◽

Takayuki Kawai ◽

Masahiko Kishi ◽

Takeyoshi Murano

Keyword(s):

Cerebrospinal Fluid ◽

Alzheimer Disease ◽

Multiple System Atrophy ◽

Parkinson Disease ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Alpha Synuclein

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Dementia with Lewy bodies

V M BEKHTEREV REVIEW OF PSYCHIATRY AND MEDICAL PSYCHOLOGY ◽

10.31363/2313-7053-2018-2-11-21 ◽

2018 ◽

pp. 11-21

Author(s):

O. S. Levin ◽

E. E. Vasenina ◽

A. Sh. Chimagomedova ◽

N. G. Dudchenko

Keyword(s):

Parkinson’S Disease ◽

Dementia With Lewy Bodies ◽

Cholinesterase Inhibitors ◽

Lewy Bodies ◽

Diagnosis And Treatment ◽

Modern Concept ◽

Historical Aspect ◽

Neurodegenerative Process ◽

Icd 10

Te lecture presents modern concept of the symptoms, diagnosis and treatment of dementia with Lewy bodies (DLB), which accounts for about 10% of cases of dementia. Te nosological status of DLB and the problem of ratio of DLB and Parkinson’s disease which, apparently, represent two phenotypic variants of one neurodegenerative process («diseases with Lewy bodies») are considered in historical aspect. Approaches to the diagnosis and coding of DLB in accordance with ICD-10 are proposed. Te role of cholinesterase inhibitors, antipsychotics, levodopa, rasagiline and other drugs in the treatment of patients with DLB is аnalyzed.

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Cerebrospinal Fluid Hypocretin and Nightmares in Dementia Syndromes

Dementia and Geriatric Cognitive Disorders Extra ◽

10.1159/000509585 ◽

2021 ◽

pp. 19-25

Author(s):

Lynn Marie Trotti ◽

Donald L. Bliwise ◽

Glenda L. Keating ◽

David B. Rye ◽

William T. Hu

Keyword(s):

Cerebrospinal Fluid ◽

Alzheimer Disease ◽

Cholinesterase Inhibitor ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Cognitively Normal ◽

Dementia Patients ◽

Sleep Questionnaires ◽

Sleep Alterations ◽

Normal Controls

Background/Aims: Hypocretin promotes wakefulness and modulates REM sleep. Alterations in the hypocretin system are increasingly implicated in dementia. We evaluated relationships among hypocretin, dementia biomarkers, and sleep symptoms in elderly participants, most of whom had dementia. Methods: One-hundred twenty-six adults (mean age 66.2 ± 8.4 years) were recruited from the Emory Cognitive Clinic. Diagnoses were Alzheimer disease (AD; n = 60), frontotemporal dementia (FTD; n = 21), and dementia with Lewy bodies (DLB; n = 20). We also included cognitively normal controls (n = 25). Participants and/or caregivers completed sleep questionnaires and lumbar puncture was performed for cerebrospinal fluid (CSF) assessments. Results: Except for sleepiness (worst in DLB) and nocturia (worse in DLB and FTD) sleep symptoms did not differ by diagnosis. CSF hypocretin concentrations were available for 87 participants and normal in 70, intermediate in 16, and low in 1. Hypocretin levels did not differ by diagnosis. Hypocretin levels correlated with CSF total τ levels only in men (r = 0.34; p = 0.02). Lower hypocretin levels were related to frequency of nightmares (203.9 ± 29.8 pg/mL in those with frequent nightmares vs. 240.4 ± 46.1 pg/mL in those without; p = 0.05) and vivid dreams (209.1 ± 28.3 vs. 239.5 ± 47.8 pg/mL; p = 0.014). Cholinesterase inhibitor use was not associated with nightmares or vivid dreaming. Conclusion: Hypocretin levels did not distinguish between dementia syndromes. Disturbing dreams in dementia patients may be related to lower hypocretin concentrations in CSF.

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Levodopa-induced dyskinesia in dementia with Lewy bodies and Parkinson disease with dementia

Neurology Clinical Practice ◽

10.1212/cpj.0000000000000703 ◽

2019 ◽

Vol 10 (2) ◽

pp. 156-161

Author(s):

Pierpaolo Turcano ◽

Cole D. Stang ◽

James H. Bower ◽

J. Eric Ahlskog ◽

Bradley F. Boeve ◽

...

Keyword(s):

Parkinson Disease ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Population Based ◽

Olmsted County ◽

Levodopa Dosage ◽

Younger Age ◽

Increased Risk ◽

Incident Cohort ◽

Median Interval

ObjectiveTo investigate the frequency of levodopa-induced dyskinesia in dementia with Lewy bodies (DLBs) and Parkinson disease with dementia (PDD) and compare these frequencies with patients with incident Parkinson disease (PD) through a population-based cohort study.MethodsWe identified all patients with DLB, PDD, and PD without dementia in a 1991–2010 population-based parkinsonism-incident cohort, in Olmsted County, Minnesota. We abstracted information about levodopa-induced dyskinesia. We compared patients with DLB and PDD with dyskinesia with patients with PD from the same cohort.ResultsLevodopa use and dyskinesia data were available for 141/143 (98.6%) patients with a diagnosis of either DLB or PDD; 87 (61.7%), treated with levodopa. Dyskinesia was documented in 12.6% (8 DLB and 3 PDD) of levodopa-treated patients. Among these patients, median parkinsonism diagnosis age was 74 years (range: 64–80 years); 63.6%, male. The median interval from levodopa initiation to dyskinesia onset was 2 years (range: 3 months–4 years); the median daily levodopa dosage was 600 mg (range: 50–1,600 mg). Dyskinesia severity led to levodopa adjustments in 5 patients, and all improved. Patients with dyskinesia were diagnosed with parkinsonism at a significantly younger age compared with patients without dyskinesia (p < 0.001). Levodopa dosage was unrelated to increased risk of dyskinesias among DLB and PDD. In contrast, 30.1% of levodopa-treated patients with PD developed dyskinesia. In age-, sex-, and levodopa dosage–adjusted models, Patients with DLB and PDD each had lower odds of developing dyskinesia than patients with PD (odds ratio = 0.42, 95% CI 0.21–0.88; p = 0.02).ConclusionsThe dyskinesia risk for levodopa-treated patients with DLB or PDD was substantially less than for levodopa-treated patients with PD.

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