[P1-243]: ALPHA-SYNUCLEIN SPECIES AS POTENTIAL CSF BIOMARKERS FOR DEMENTIA WITH LEWY BODIES

2017 ◽  
Vol 13 (7S_Part_7) ◽  
pp. P338-P338 ◽  
Author(s):  
Inger van Steenoven ◽  
Nour K. Majbour ◽  
Nishant N. Vaikath ◽  
Henk W. Berendse ◽  
Wiesje M. van der Flier ◽  
...  
1999 ◽  
Vol 58 (5) ◽  
pp. 553
Author(s):  
E Gómez-Tortosa ◽  
K L Newell ◽  
M C Irizarry ◽  
M Albert ◽  
J H Growdon ◽  
...  

2019 ◽  
Vol 20 (19) ◽  
pp. 4674 ◽  
Author(s):  
Inger van Steenoven ◽  
Barbara Noli ◽  
Cristina Cocco ◽  
Gian-Luca Ferri ◽  
Patrick Oeckl ◽  
...  

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.


Medicina ◽  
2012 ◽  
Vol 48 (1) ◽  
pp. 1 ◽  
Author(s):  
Jūratė Macijauskienė ◽  
Vita Lesauskaitė

Dementia with Lewy bodies was first recognized as a separate entity about 30 years ago. The prevalence varies from 0% to 5% in the general population, and this disease accounts for 0% to 30.5% of all dementia cases. Dementia with Lewy bodies is considered the second most common cause of degenerative dementia after Alzheimer’s disease. The disease is characterized by alpha-synuclein immunoreactive protein deposits in both neurons and glial cells. The protein deposits are especially prominent in dopaminergic neurons, where they can be detected using conventional histological stains, such as hematoxylin and eosin, and are commonly referred to as Lewy bodies. The diagnosis of dementia with Lewy bodies is based on the presence of dementia as well as 2 of the following 3 core diagnostic features: 1) fluctuating cognition, 2) visual hallucinations, and 3) movement disorder. Diagnostic tests include laboratory data, structural and functional imaging, and electroencephalography. Differential diagnosis of dementia with Lewy bodies focuses on other later life dementia syndromes, other parkinsonian diseases (Parkinson’s disease, progressive supranuclear palsy, corticobasal degeneration), and primary psychiatric illnesses. There is type 1b evidence to support treatment with cholinesterase inhibitors. Glutamatergic and dopaminergic therapies are used as well. Standard neuroleptics are contraindicated, and atypical agents should be used cautiously. Nonpharmacologic measures – therapeutic environment, psychological and social support, physical activity, behavioral management strategies, caregivers’ education and support, and different services – could be suggested.


2019 ◽  
Vol 78 (10) ◽  
pp. 877-890 ◽  
Author(s):  
Norihito Uemura ◽  
Maiko T Uemura ◽  
Angela Lo ◽  
Fares Bassil ◽  
Bin Zhang ◽  
...  

Abstract Synucleinopathies are composed of Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Alpha-synuclein (α-Syn) forms aggregates mainly in neurons in PD and DLB, while oligodendroglial α-Syn aggregates are characteristic of MSA. Recent studies have demonstrated that injections of synthetic α-Syn preformed fibrils (PFFs) into the brains of wild-type (WT) animals induce intraneuronal α-Syn aggregates and the subsequent interneuronal transmission of α-Syn aggregates. However, injections of α-Syn PFFs or even brain lysates of patients with MSA have not been reported to induce oligodendroglial α-Syn aggregates, raising questions about the pathogenesis of oligodendroglial α-Syn aggregates in MSA. Here, we report that WT mice injected with mouse α-Syn (m-α-Syn) PFFs develop neuronal α-Syn pathology after short postinjection (PI) intervals on the scale of weeks, while oligodendroglial α-Syn pathology emerges after longer PI intervals of several months. Abundant oligodendroglial α-Syn pathology in white matter at later time points is reminiscent of MSA. Furthermore, comparison between young and aged mice injected with m-α-Syn PFFs revealed that PI intervals rather than aging correlate with oligodendroglial α-Syn aggregation. These results provide novel insights into the pathological mechanisms of oligodendroglial α-Syn aggregation in MSA.


2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Mirko Bibl ◽  
Hermann Esselmann ◽  
Piotr Lewczuk ◽  
Claudia Trenkwalder ◽  
Markus Otto ◽  
...  

We studied the diagnostic value of CSF Aβ42/tau versus low Aβ1–42% and high Aβ1–40ox% levels for differential diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), respectively. CSF of 45 patients with AD, 15 with DLB, 21 with Parkinson's disease dementia (PDD), and 40 nondemented disease controls (NDC) was analyzed by Aβ-SDS-PAGE/immunoblot and ELISAs (Aβ42 and tau). Aβ42/tau lacked specificity in discriminating AD from DLB and PDD. Best discriminating biomarkers were Aβ1–42% and Aβ1–40ox% for AD and DLB, respectively. AD and DLB could be differentiated by both Aβ1–42% and Aβ1–40ox% with an accuracy of 80% at minimum. Thus, we consider Aβ1–42% and Aβ1–40ox% to be useful biomarkers for AD and DLB, respectively. We propose further studies on the integration of Aβ1–42% and Aβ1–40ox% into conventional assay formats. Moreover, future studies should investigate the combination of Aβ1–40ox% and CSF alpha-synuclein for the diagnosis of DLB.


2010 ◽  
Vol 2010 ◽  
pp. 1-17 ◽  
Author(s):  
Elizabeta B. Mukaetova-Ladinska ◽  
Rachael Monteith ◽  
Elaine K. Perry

More than 750,000 of the UK population suffer from some form of cognitive impairment and dementia. Of these, 5–20% will have Dementia with Lewy Bodies (DLB). Clinico-pathological studies have shown that it is the low frequency of DLB clinical core features that makes the DLB diagnosis hardly recognisable during life, and easily misdiagnosed for other forms of dementia. This has an impact on the treatment and long-term care of the affected subjects. Having a biochemical test, based on quantification of a specific DLB biomarker within Cerebrospinal Fluid (CSF) could be an effective diagnostic method to improve the differential diagnosis. Although some of the investigated DLB CSF biomarkers are well within the clinical criteria for sensitivity and specificity (90%), they all seem to be confounded by the contradictory data for each of the major groups of biomarkers (-synuclein, tau and amyloid proteins). However, a combination of CSF measures appear to emerge, that may well be able to differentiate DLB from other dementias: -synuclein reduction in early DLB, a correlation between CSF -synuclein and A42 measures (characteristic for DLB only), and t-tau and p-tau181 profile (differentiating AD from DLB).


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