Platelet miRNA bio-signature discriminates between dementia with Lewy bodies and Alzheimer disease

Gámez-Valero, Ana; Campdelacreu, Jaume; Vilas, Dolores; Ispierto, Lourdes; Samaniego, Daniela; Gascón‐Bayarri, Jordi; Rizzoli, René; Álvarez, Ramiro; Armengol, María Pilar; Borràs, Francesc E.; Beyer, Katrin

doi:10.1101/2020.05.04.075713

Cited by 2 publications

(4 citation statements)

References 45 publications

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“…Lastly, let‐7c was not described in PD previously, but other members of the let‐7 family showed deregulation in PD 32,43,47‐49 . In summary, most of the 12 biosignature miRNAs were earlier reported in α‐synucleinopathy 5‐7,10,21,22,33,36‐42 . This is relevant given that, if validated, our findings may have implications for other PD at‐risk cohorts, such as individuals with hyposmia or LRRK2 or GBA asymptomatic mutation carriers.…”

Section: Discussionsupporting

confidence: 55%

“… 32 , 43 , 47 , 48 , 49 In summary, most of the 12 biosignature miRNAs were earlier reported in α‐synucleinopathy. 5 , 6 , 7 , 10 , 21 , 22 , 33 , 36 , 37 , 38 , 39 , 40 , 41 , 42 This is relevant given that, if validated, our findings may have implications for other PD at‐risk cohorts, such as individuals with hyposmia or LRRK2 or GBA asymptomatic mutation carriers.…”

Section: Discussionmentioning

confidence: 74%

“…Ten of the 12 biosignature miRNAs were earlier deregulated in different PD or DLB biospecimens. In LBD peripheral tissues, miR‐19b‐3p, 8 , 36 , 37 miR‐29c‐3p, 7 , 8 , 37 , 38 miR‐221‐3p, 6 , 7 , 37 miR‐24‐3p, 5 , 36 and miR‐451a 37 were reported in PD serum; miR‐19b‐3p, miR‐29c‐3p, and miR‐361 in PD or early‐stage PD peripheral blood mononuclear cells 33 , 39 , 40 ; miR‐451 in PD leukocytes 41 ; miR‐25 in DLB platelets 42 ; and miR‐22, 21 miR‐4505, 22 and miR‐140‐3p 10 in PD whole blood. Other biosignature miRNAs were described in the central nervous system (CNS), such as miR‐19b‐3p, miR‐22, miR‐29c, 43 and miR‐24 44 in PD CSF; or miR‐221 and miR‐425‐5p 45 , 46 in PD brain.…”

Section: Discussionmentioning

confidence: 99%

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Serum MicroRNAs Predict Isolated Rapid Eye Movement Sleep Behavior Disorder and Lewy Body Diseases

et al. 2022

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Background Isolated rapid eye movement sleep behavior disorder (IRBD) is a well‐established clinical risk factor for Lewy body diseases (LBDs), such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Objective To elucidate whether serum microRNA (miRNA) deregulation in IRBD can antedate the diagnosis of LBD by performing a longitudinal study in different progression stages of IRBD before and after LBD diagnosis and assessing the predictive performance of differentially expressed miRNAs by machine learning–based modeling. Methods Using genome‐wide miRNA analysis and real‐time quantitative polymerase chain reaction validation, we assessed serum miRNA profiles from patients with IRBD stratified by dopamine transporter (DaT) single‐photon emission computed tomography into DaT‐negative IRBD (n = 17) and DaT‐positive IRBD (n = 21), IRBD phenoconverted into LBD (n = 13), and controls (n = 20). Longitudinally, we followed up the IRBD cohort by studying three time point serum samples over 26 months. Results We found sustained cross‐sectional and longitudinal deregulation of 12 miRNAs across the RBD continuum, including DaT‐negative IRBD, DaT‐positive IRBD, and LBD phenoconverted IRBD (let‐7c‐5p, miR‐19b‐3p, miR‐140, miR‐22‐3p, miR‐221‐3p, miR‐24‐3p, miR‐25‐3p, miR‐29c‐3p, miR‐361‐5p, miR‐425‐5p, miR‐4505, and miR‐451a) (false discovery rate P < 0.05). Age‐ and sex‐adjusted predictive modeling based on the 12 differentially expressed miRNA biosignatures discriminated IRBD and PD or DLB from controls with an area under the curve of 98% (95% confidence interval: 89–99%). Conclusions Besides clinical diagnosis of IRBD or imaging markers such as DaT single‐photon emission computed tomography, specific miRNA biosignatures alone hold promise as progression biomarkers for patients with IRBD for predicting PD and DLB clinical outcomes. Further miRNA studies in other PD at‐risk populations, such as LRRK2 mutation asymptomatic carriers or hyposmic subjects, are warranted. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

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Serum MicroRNAs Predict Isolated Rapid Eye Movement Sleep Behavior Disorder and Lewy Body Diseases

et al. 2022

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“…Several studies have been so far reported studying miRNAs purified by different biological samples. Gamez-Valero et al [ 131 ], by profiling the whole miRNA transcriptome from platelet belonging to DLB, AD, and PD patients as well as to healthy controls (HC), identified a 7-miRNA biosignature with a high potential for the differential diagnosis between DLB and AD. In particular, they detected 3 groups of miRNAs, each specifically deregulated in one of the analyzed disorders.…”

Section: Mirna Expression Profilingmentioning

confidence: 99%

Genetic Architecture and Molecular, Imaging and Prodromic Markers in Dementia with Lewy Bodies: State of the Art, Opportunities and Challenges

Combi

Salsone

Clara

et al. 2021

IJMS

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Dementia with Lewy bodies (DLB) is one of the most common causes of dementia and belongs to the group of α-synucleinopathies. Due to its clinical overlap with other neurodegenerative disorders and its high clinical heterogeneity, the clinical differential diagnosis of DLB from other similar disorders is often difficult and it is frequently underdiagnosed. Moreover, its genetic etiology has been studied only recently due to the unavailability of large cohorts with a certain diagnosis and shows genetic heterogeneity with a rare contribution of pathogenic mutations and relatively common risk factors. The rapid increase in the reported cases of DLB highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods proposed by the International DLB consortium rely on a list of criteria that comprises both clinical observations and the use of biomarkers. Herein, we summarize the up-to-now reported knowledge on the genetic architecture of DLB and discuss the use of prodromal biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.

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Platelet miRNA bio-signature discriminates between dementia with Lewy bodies and Alzheimer disease

Cited by 2 publications

References 45 publications

Serum MicroRNAs Predict Isolated Rapid Eye Movement Sleep Behavior Disorder and Lewy Body Diseases

Serum MicroRNAs Predict Isolated Rapid Eye Movement Sleep Behavior Disorder and Lewy Body Diseases

Genetic Architecture and Molecular, Imaging and Prodromic Markers in Dementia with Lewy Bodies: State of the Art, Opportunities and Challenges

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