A new potential biomarker for dementia with Lewy bodies

Neurology ◽  
2017 ◽  
Vol 89 (4) ◽  
pp. 318-326 ◽  
Author(s):  
Vincenzo Donadio ◽  
Alex Incensi ◽  
Giovanni Rizzo ◽  
Sabina Capellari ◽  
Roberta Pantieri ◽  
...  
Keyword(s):  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Nerve Fibers ◽  
Class Iii ◽  
Skin Sample ◽  
Potential Biomarker ◽  
Autonomic Dysfunctions ◽  
Skin Biopsies ◽  
Small Nerve

Objective:To investigate whether (1) phosphorylated α-synuclein (p-syn) deposits in skin nerves could be useful in differentiating dementia with Lewy bodies (DLB) from different forms of dementia and (2) small fiber neuropathy (SFN) is associated with DLB.Methods:We studied 18 well-characterized patients with DLB (11 with autonomic dysfunction), 23 patients with nonsynucleinopathy dementia (NSD; 13 with young-onset Alzheimer disease dementia, 6 frontotemporal dementia, and 4 vascular dementia), and 25 healthy controls. All participants underwent skin biopsies from proximal (i.e., cervical) and distal (i.e., thigh and distal leg) sites to study small nerve fibers and deposits of p-syn, considered the pathologic form of α-synuclein.Results:No p-syn was detected in any skin sample in patients with NSD and controls but was found in all patients with DLB. SFN was found in patients with DLB and the autonomic denervation of skin was more severe in patients with autonomic dysfunctions.Conclusions:(1) In autonomic skin nerves, p-syn is a sensitive biomarker for DLB diagnosis, helping to differentiate DLB from other forms of dementia, although this needs to be confirmed in a larger, more representative sample; and (2) skin autonomic neuropathy is part of the DLB pathology and may contribute to autonomic symptoms.Classification of evidence:This study provides Class III evidence that p-syn in skin nerve fibers on skin biopsy accurately distinguishes DLB from other forms of dementia.

Autonomic dysfunctions in dementia with Lewy bodies

2003 ◽  
Vol 250 (5) ◽  
pp. 530-533 ◽  
Author(s):  
Yoshihiko Horimoto ◽  
Mitsuhiro Matsumoto ◽  
Hiroyasu Akatsu ◽  
Hiroyuki Ikari ◽  
Kiyohide Kojima ◽  
...  
Keyword(s):  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Autonomic Dysfunctions

scholarly journals VGF Peptides in Cerebrospinal Fluid of Patients with Dementia with Lewy Bodies

2019 ◽  
Vol 20 (19) ◽  
pp. 4674 ◽  
Author(s):  
Inger van Steenoven ◽  
Barbara Noli ◽  
Cristina Cocco ◽  
Gian-Luca Ferri ◽  
Patrick Oeckl ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Analytical Methods ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Disease Stage ◽  
Selected Reaction Monitoring ◽  
Csf Biomarkers ◽  
Potential Biomarker ◽  
Proteomic Study

In a previous proteomic study, we identified the neurosecretory protein VGF (VGF) as a potential biomarker for dementia with Lewy bodies (DLB). Here, we extended the study of VGF by comparing levels in cerebrospinal fluid (CSF) from 44 DLB patients, 20 Alzheimer’s disease (AD) patients, and 22 cognitively normal controls selected from the Amsterdam Dementia Cohort. CSF was analyzed using two orthogonal analytical methods: (1) In-house-developed quantitative ELISA and (2) selected reaction monitoring (SRM). We further addressed associations of VGF with other CSF biomarkers and cognition. VGF levels were lower in CSF from patients with DLB compared to either AD patients or controls. VGF was positively correlated with CSF tau and α-synuclein (0.55 < r < 0.75), but not with Aβ1-42. In DLB patients, low VGF levels were related to a more advanced cognitive decline at time of first presentation, whereas high levels of VGF were associated with steeper subsequent longitudinal cognitive decline. Hence, CSF VGF levels were lower in DLB compared to both AD and controls across different analytical methods. The strong associations with cognitive decline further points out VGF as a possible disease stage or prognostic marker for DLB.

scholarly journals Focal atrophy on MRI and neuropathologic classification of dementia with Lewy bodies

Neurology ◽  
2012 ◽  
Vol 79 (6) ◽  
pp. 553-560 ◽  
Author(s):  
K. Kantarci ◽  
T. J. Ferman ◽  
B. F. Boeve ◽  
S. D. Weigand ◽  
S. Przybelski ◽  
...  
Keyword(s):  
Dementia With Lewy Bodies ◽  
Lewy Bodies

Validation of a new assay for α-synuclein detection in cerebrospinal fluid

2017 ◽  
Vol 55 (2) ◽  
Author(s):  
Marthe Gurine Førland ◽  
Annika Öhrfelt ◽  
Linn Silje Oftedal ◽  
Ole-Bjørn Tysnes ◽  
Jan Petter Larsen ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Neurodegenerative Diseases ◽  
Dementia With Lewy Bodies ◽  
Limit Of Detection ◽  
Lewy Bodies ◽  
High Sensitivity ◽  
Cross Reactivity ◽  
Additional Method ◽  
Potential Biomarker ◽  
Assay Protocol

AbstractBackground:Abnormal α-synuclein aggregation and deposition is the pathological hallmark of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), but is also found in Alzheimer disease (AD). Therefore, there is a gaining interest in α-synuclein in cerebrospinal fluid (CSF) as potential biomarker for these neurodegenerative diseases. To broaden the available choices of α-synuclein measurement in CSF, we developed and validated a new assay for detecting total α-synuclein.Methods:This novel ELISA uses commercially available antibodies and is based on electrochemiluminescence technology. The assay protocol is straightforward, with short and simple incubation steps, and requires only small amounts of CSF. We validated this assay for precision, parallelism, dilution linearity, specificity, and spike recovery. We further compared it to the newly validated α-synuclein assay from BioLegend by analyzing a set of 50 CSF samples with both assays.Results:The new assay quantifies α-synuclein in CSF with a lower limit of detection of 36.3 pg/mL and shows no cross-reactivity with human β- and γ-synuclein. Results of dilution linearity, parallelism, spike recovery, and precision classify this assay as well suited for α-synuclein detection in human CSF samples.Conclusions:We present a novel assay based on freely available components to quantify total α-synuclein in CSF as an additional method for α-synuclein as a biomarker in neurodegenerative diseases. The assay convinces with its simple and convenient protocol paired with high sensitivity.

scholarly journals Streamlined alpha-synuclein RT-QuIC assay for various biospecimens in Parkinson’s disease and dementia with Lewy bodies

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Connor Bargar ◽  
Wen Wang ◽  
Steven A. Gunzler ◽  
Alexandra LeFevre ◽  
Zerui Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Peripheral Tissues ◽  
Potential Biomarker ◽  
Wide Range ◽  
Different Types ◽  
Diagnostic Values

AbstractDefinitive diagnosis of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) relies on postmortem finding of disease-associated alpha-synuclein (αSynD) as misfolded protein aggregates in the central nervous system (CNS). The recent development of the real-time quaking induced conversion (RT-QuIC) assay for ultrasensitive detection of αSynD aggregates has revitalized the diagnostic values of clinically accessible biospecimens, including cerebrospinal fluid (CSF) and peripheral tissues. However, the current αSyn RT-QuIC assay platforms vary widely and are thus challenging to implement and standardize the measurements of αSynD across a wide range of biospecimens and in different laboratories. We have streamlined αSyn RT-QuIC assay based on a second generation assay platform that was assembled entirely with commercial reagents. The streamlined RT-QuIC method consisted of a simplified protocol requiring minimal hands-on time, and allowing for a uniform analysis of αSynD in different types of biospecimens from PD and DLB. Ultrasensitive and specific RT-QuIC detection of αSynD aggregates was achieved in million-fold diluted brain homogenates and in nanoliters of CSF from PD and DLB cases but not from controls. Comparative analysis revealed higher seeding activity of αSynD in DLB than PD in both brain homogenates and CSF. Our assay was further validated with CSF samples of 214 neuropathologically confirmed cases from tissue repositories (88 PD, 58 DLB, and 68 controls), yielding a sensitivity of 98% and a specificity of 100%. Finally, a single RT-QuIC assay protocol was employed uniformly to detect seeding activity of αSynD in PD samples across different types of tissues including the brain, skin, salivary gland, and colon. We anticipate that our streamlined protocol will enable interested laboratories to easily and rapidly implement the αSyn RT-QuIC assay for various clinical specimens from PD and DLB. The utilization of commercial products for all assay components will improve the robustness and standardization of the RT-QuIC assay for diagnostic applications across different sites. Due to ultralow sample consumption, the ultrasensitive RT-QuIC assay will facilitate efficient use and sharing of scarce resources of biospecimens. Our streamlined RT-QuIC assay is suitable to track the distribution of αSynD in CNS and peripheral tissues of affected patients. The ongoing evaluation of RT-QuIC assay of αSynD as a potential biomarker for PD and DLB in clinically accessible biospecimens has broad implications for understanding disease pathogenesis, improving early and differential diagnosis, and monitoring therapeutic efficacies in clinical trials.

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