scholarly journals Platelet miRNA Biosignature Discriminates between Dementia with Lewy Bodies and Alzheimer’s Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1272
Author(s):  
Ana Gámez-Valero ◽  
Jaume Campdelacreu ◽  
Dolores Vilas ◽  
Lourdes Ispierto ◽  
Jordi Gascón-Bayarri ◽  
...  

Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia, after Alzheimer’s disease (AD), and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a seven-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based biosignature, which distinguishes DLB from AD.

2020 ◽  
Author(s):  
Ana Gámez-Valero ◽  
Jaume Campdelacreu ◽  
Dolores Vilas ◽  
Lourdes Ispierto ◽  
Daniela Samaniego ◽  
...  

Abstract Background Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia after Alzheimer’s disease (AD) and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets have been previously related to neurodegeneration. They contain microRNAs (miRNAs), and their analysis may provide disease biomarkers. Methods Small RNAs from platelets of DLB patients and controls were analyzed by Next Generation Sequencing (NGS), and miRNAs deregulated in DLB were selected. Expression of these miRNAs was then determined and validated by LNA-based qRT-PCR in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Their predictive diagnostic potential was calculated by ROC curve analysis. miRTarbase and miRGate were used for target prediction. Results We profiled the whole platelet miRNA transcriptome from 7 DLB patients and 7 controls using NGS. Twenty-two selected miRNAs were further validated in independent studies (2017–2019) including DLB (n = 59), AD (n = 28), and PD (n = 24) patients, and control individuals (n = 51). Our results demonstrated downregulated expression levels for hsa-let-7d-5p (fold change 0.14; p = 0.006), hsa-miR-132-5p (0.12; p = 0.0015), hsa-miR-142-3p (0.07; p = 0.00047), hsa-miR-146a-5p (0.07; p = 0.00035), hsa-miR-150-5p (0.10; p = 0.0098), hsa-miR-25-3p (0.13; p = 0.0019) and hsa-miR-26b-5p (0.09; p = 0.0014) in DLB compared to AD. ROC curve for this seven-miRNA biosignature yielded an area under the curve (AUC) of 1. Both hsa-miR-142-3p and hsa-miR-150-5p, were down-regulated in DLB compared to controls (AUC = 0.85). Comparing AD and controls, miRNAs hsa-miR-132-5p, hsa-miR-146a-5p, hsa-miR-25-3p, and hsa-miR-6747-3p were up-regulated in AD (AUC = 0.94); and hsa-miR-128-3p and hsa-miR-139-5p were down-regulated in PD compared to controls (AUC = 0.81). Predictive target analysis identified three disease-specific pathway clusters as a result of platelet-miRNA deregulation. In DLB, pathways related to gene expression and small RNA metabolism; in AD, pathways related to stress response and RNA stress granules; and in PD pathways related to protein phosphorylation, metabolism and degradation were identified. Conclusion A platelet-associated bio-signature composed of 7 miRNAs is highly specific and sensitive for distinguishing DLB from AD.


2018 ◽  
Vol 46 (3-4) ◽  
pp. 168-179 ◽  
Author(s):  
Frederikke Jeppesen Kragh ◽  
Marie Bruun ◽  
Esben Budtz-Jørgensen ◽  
Lena Elisabeth Hjermind ◽  
Robin Schubert ◽  
...  

Background: This study examines the efficacy of using quantitative measurements of motor dysfunction, compared to clinical ratings, in Alzheimer’s disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Methods: In this cross-sectional study, 49 patients with a diagnosis of AD (n = 17), FTD (n = 19), or DLB (n = 13) were included and underwent cognitive testing, clinical motor evaluation, and quantitative motor tests: pronation/supination hand tapping, grasping and lifting, and finger and foot tapping. Results: Our results revealed significantly higher Q-Motor values in pronation/supination and in grip lift force assessment in AD, FTD, and DLB compared to healthy controls (HC). Q-Motor values detected significant differences between AD and HC, while clinical ratings did not. Conclusion: Our results suggest that quantitative measurements provide more objective and sensitive measurements of motor dysfunction in dementia.


2020 ◽  
Author(s):  
Ana Gámez-Valero ◽  
Jaume Campdelacreu ◽  
Dolores Vilas ◽  
Lourdes Ispierto ◽  
Daniela Samaniego ◽  
...  

ABSTRACTDementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia after Alzheimer’s disease (AD) and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a 7-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based bio-signature, which distinguishes DLB from AD.The paper explainedProblemDementia with Lewy bodies (DLB) presents pathological and clinical overlap with both Alzheimer’s (AD) and Parkinson’s disease (PD), which impairs its correct diagnosis. Although numerous papers report peripheral biomarkers for AD, well-established biomarkers for DLB distinguishing it from AD are still missing. Platelet miRNA transcriptome was analyzed in several works, but their putative role as disease biomarkers for neurological disorders has not been assessed. It would be of paramount importance to establish a blood-based bio-signature as a minimally invasive mean for DLB diagnosis, improving differentiation of DLB patients from controls and AD.ResultsOur study revealed that platelet miRNAs might be promising biomarkers for the correct diagnosis of DLB stratifying patients in comparison with overlapping disorders, especially AD, and may help to highlight possible disease-related processes. In this cross-sectional study, which includes 162 individuals (DLB, AD, PD and healthy controls), platelet-associated miRNA content was disease group-specific. Three different miRNA sets together with their predicted targeted pathways were defined.ImpactThis study suggests that platelet miRNA may serve as DLB biomarker allowing the correct diagnosis and stratification in an easily-applied manner in clinical settings, and may help to highlight possible disease-related processes.


2020 ◽  
Vol 10 (2) ◽  
pp. 74-85
Author(s):  
Yuka Oishi ◽  
Toru Imamura ◽  
Tatsuo Shimomura ◽  
Kyoko Suzuki

Introduction: Although various visual function deficits have been reported in patients with Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB), vegetable freshness perception has not been thoroughly examined. Objective: To investigate vegetable freshness perception in patients with AD and DLB and to clarify the relationship between vegetable freshness perception and various visuoperceptual functions. Methods: We enrolled 37 patients with probable DLB, 58 patients with probable AD, and 32 age-matched healthy controls. We assessed vegetable freshness perception and visuoperceptual functions, including vegetable brightness perception, contrast sensitivity, color perception, and stereopsis. Patients with DLB showed disproportionate deficits in vegetable freshness perception and vegetable luminance perception compared to patients with AD and controls. Analyses of the groups with higher and lower vegetable freshness perceptions revealed significant differences in contrast sensitivity and visual texture recognition. Results: In the vegetable freshness test, we found significant differences among the 3 groups (F = 30.029, p < 0.0001); the extent of impairment in patients with DLB was greater than that in patients with AD. In patients with DLB, the vegetable freshness judgments were significantly correlated with texture judgment scores and contrast sensitivity. Conclusion: Our findings revealed significantly impaired vegetable freshness perception in patients with DLB. Vegetable freshness perception may be related to visual texture recognition in patients with DLB.


2016 ◽  
Vol 2016 ◽  
pp. 1-11
Author(s):  
Stephanie Yamin ◽  
Arne Stinchcombe ◽  
Sylvain Gagnon

Purpose. Alzheimer’s disease (AD) and dementia with Lewy Bodies (DLB) constitute two of the most common forms of dementia in North America. Driving is a primary means of mobility among older adults and the risk of dementia increases with advanced age. The purpose of this paper is to describe the cognitive profile of licensed drivers with mild AD and mild DLB.Method. Licensed drivers with mild AD, mild DLB, and healthy controls completed neuropsychological tests measuring general cognition, attention, visuospatial/perception, language, and cognitive fluctuations.Results. The results showed differences between healthy controls and demented participants on almost all neuropsychological measures. Participants with early DLB were found to perform significantly worse on some measures of attention and visuospatial functioning in comparison with early AD.Discussion. Future research should examine the relationship between neuropsychological measures and driving outcomes among individuals with mild AD and mild DLB.


2011 ◽  
Vol 22 (1) ◽  
pp. 1-9
Author(s):  
Rebecca J Hancock

SummaryAlzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the two most common types of degenerative dementia. It has been questioned whether they are totally separate conditions, or whether they are in fact both part of a spectrum of a more general neurodegenerative disease. Fluctuating cognition and parkinsonism are key features of DLB, but atypical in AD which is characterized by progressive amnesia, aphasia, agnosia and apraxia. Neuropsychiatric disturbances also seem to be more common in DLB. The main neuropathological features of DLB are Lewy bodies, and in AD are senile plaques and neurofibrillary tangles, though some overlap has been found. A key finding of neuroimaging studies is that there is relative preservation of brain volume in DLB patients compared with AD patients, particularly of temporal lobe structures. There are also profound reductions in striatal dopamine transport in DLB, demonstrated by single photon emission computerized tomography (SPECT) imaging. Whilst there are some distinct differences between AD and DLB, further research is needed to greater define the distinctions between these two conditions.


2021 ◽  
pp. 155005942199714
Author(s):  
Lucia Zinno ◽  
Anna Negrotti ◽  
Chiara Falzoi ◽  
Giovanni Messa ◽  
Matteo Goldoni ◽  
...  

Introduction. An easily accessible and inexpensive neurophysiological technique such as conventional electroencephalography may provide an accurate and generally applicable biomarker capable of differentiating dementia with Lewy bodies (DLB) from Alzheimer’s disease (AD) and Parkinson’s disease-associated dementia (PDD). Method. We carried out a retrospective visual analysis of resting-state electroencephalography (EEG) recording of 22 patients with a clinical diagnosis of 19 probable and 3 possible DLB, 22 patients with probable AD and 21 with PDD, matched for age, duration, and severity of cognitive impairment. Results. By using the grand total EEG scoring method, the total score and generalized rhythmic delta activity frontally predominant (GRDAfp) alone or, even better, coupled with a slowing of frequency of background activity (FBA) and its reduced reactivity differentiated DLB from AD at an individual level with an high accuracy similar to that obtained with quantitative EEG (qEEG). GRDAfp alone could also differentiate DLB from PDD with a similar level of diagnostic accuracy. AD differed from PDD only for a slowing of FBA. The duration and severity of cognitive impairment did not differ between DLB patients with and without GRDAfp, indicating that this abnormal EEG pattern should not be regarded as a disease progression marker. Conclusions. The findings of this investigation revalorize the role of conventional EEG in the diagnostic workup of degenerative dementias suggesting the potential inclusion of GRDAfp alone or better coupled with the slowing of FBA and its reduced reactivity, in the list of supportive diagnostic biomarkers of DLB.


2007 ◽  
Vol 26 (3) ◽  
pp. 414-419 ◽  
Author(s):  
John R. Merory ◽  
Joanne E. Wittwer ◽  
Christopher C. Rowe ◽  
Kate E. Webster

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