MicroRNA deregulation and chemotaxis and phagocytosis impairment in Alzheimer's disease

Guedes, Joana; Santana, Isabel; Cunha, Catarina; Duro, Diana; Almeida, Maria Rosário; Cardoso, Ana M.; Lima, Maria C. Pedroso de

doi:10.1016/j.dadm.2015.11.004

Cited by 60 publications

(47 citation statements)

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“…Therefore the lack of assessment of AD molecular correlates such as classical CSF biomarkers leads to doubts as to the homogeneity and identity of the MCI groups, and makes interpreting the results difficult. In fact, there is a discrepancy in existing data of blood-based miRNAs in MCI patients because MCI was either considered as a dementia type/stage different than AD [22, 23, 39, 43] or MCI was assumed to represent early AD, and was included in the analysis together with probable AD as one disease group [20, 21]. Some other authors attempted to stratify the MCI group according to dementia psychological assays and PIB-PET brain imaging, but the classification omitted CSF markers and thus cannot be referred to such biochemical measures [41, 68–70].…”

Section: Discussionmentioning

confidence: 99%

“…Other miRNAs were reported in single studies: hsa-miR-301a-3p [21], hsa-miR-103a-3p and hsa-let-7d-3p [22], hsa-miR-200a-3p [30], hsa-miR-15b-3p [41], hsa-miR-502-3p [28]. Moreover, hsa-miR-22-5p [27], hsa-miR-186-5p and hsa-miR-30c-5p [28] were found significantly deregulated only in patients with later AD, and the remaining 10 miRNAs were found in early AD (MCI-AD) patients: hsa-miR-342-3p [24, 41], hsa-miR-146a-5p [34, 43], hsa-miR-106a-5p [41, 84], hsa-miR-339-3p and hsa-miR-339-3p [37], hsa-miR-18b-5p [41], hsa-miR-338-3p [29], hsa-miR-660-5p [28], hsa-miR-150-5p [29], hsa-miR-27b-3p [39]. Thus, our results strongly support the potential of miRNAs as plasma-based AD biomarkers in AD, assuming strict standardization of methodology.…”

Section: Discussionmentioning

confidence: 99%

“…This is the case for the following miRNAs in our study: hsa-miR-200a-3p, hsa-let-7f-5p, hsa-miR-146a-5p, hsa-miR-339-5p, hsa-miR-339-3p, hsa-miR-27b-3p. The previously reported miRNAs were, respectively: hsa-miR-200a [30], hsa-let-7f [30], hsa-miR-146a [34, 43], hsa-miR-339 [37], hsa-miR-27b [39]. …”

Section: Methodsmentioning

confidence: 99%

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Profile of 6 microRNA in blood plasma distinguish early stage Alzheimer’s disease patients from non-demented subjects

et al. 2017

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Alzheimers disease (AD) is the most common age-related dementia. Among its major challenges is identifying molecular signatures characteristic for the early AD stage in patients with Mild Cognitive Impairment (MCI-AD), which could serve for deciphering the AD pathomechanism and also as non-invasive, easy-to-access biomarkers. Using qRT-PCR we compared the microRNA (miRNA) profiles in blood plasma of 15 MCI-AD patients, whose diagnoses were confirmed by cerebrospinal fluid (CSF) biomarkers, with 20 AD patients and 15 non-demented, age-matched individuals (CTR).To minimize methodological variability, we adhered to standardization of blood and CSF assays recommended by the international Joint Programming for Neurodegenerative Diseases (JPND) BIOMARKAPD consortium, and we employed commercially available Exiqon qRT-PCR-assays. In the first screening, we assessed 179 miRNAs of plasma. We confirmed 23 miRNAs reported earlier as AD biomarker candidates in blood and found 26 novel differential miRNAs between AD and control subjects. For representative 15 differential miRNAs, the TargetScan, MirTarBase and KEGG database analysis indicated putative protein targets among such AD hallmarks as MAPT (Tau), proteins involved in amyloidogenic proteolysis, and in apoptosis. These 15 miRNAs were verified in separate, subsequent subject groups. Finally, 6 miRNAs (3 not yet reported in AD context and 3 reported in AD blood) were selected as the most promising biomarker candidates differentiating early AD from controls with the highest fold changes (from 1.32 to 14.72), consistent significance, specificities from 0.78 to 1 and sensitivities from 0.75 to 1. (patent pending, PCT/IB2016/052440).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Profile of 6 microRNA in blood plasma distinguish early stage Alzheimer’s disease patients from non-demented subjects

et al. 2017

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“…Reports on TREM2 mRNA levels at the pre-dementia stage remain scarce. To our knowledge, only one other study has looked at TREM2 expression in MCI subjects, finding higher TREM2 mRNA expression in blood-derived monocytes and monocyte-derived macrophages in MCI compared to AD and controls [12]. Furthermore, none of these studies looked at correlation with neuroimaging, and it remains unknown how changes in TREM2 mRNA relate to brain structural changes in AD and MCI.…”

Section: Introductionmentioning

confidence: 99%

Higher Peripheral TREM2 mRNA Levels Relate to Cognitive Deficits and Hippocampal Atrophy in Alzheimer’s Disease and Amnestic Mild Cognitive Impairment

Tan

Vipin

et al. 2017

JAD

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“…Blood-based biomarkers have been studied extensively in AD with regards to diagnostics (81–84), risk prediction (85), understanding the complexity of the pathobiology (86, 87). Within the precision medicine area, the primary need is for companion diagnostic assays (CDx) that not only aid in the identification of which patients are most likely to respond to specific interventions, but also to rule out those patients who may suffer from safety and tolerability issues (75).…”

Section: Discovery Development and Validation Of Pathophysiologicalmentioning

confidence: 99%

Precision Medicine - The Golden Gate for Detection, Treatment and Prevention of Alzheimer’s Disease

Hampel¹,

O’Bryant

Castrillo

et al. 2016

J Prev Alz Dis

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During this decade, breakthrough conceptual shifts have commenced to emerge in the field of Alzheimer’s disease (AD) recognizing risk factors and the non-linear dynamic continuum of complex pathophysiologies amongst a wide dimensional spectrum of multi-factorial brain proteinopathies/neurodegenerative diseases. As is the case in most fields of medicine, substantial advancements in detecting, treating and preventing AD will likely evolve from the generation and implementation of a systematic precision medicine strategy. This approach will likely be based on the success found from more advanced research fields, such as oncology. Precision medicine will require integration and transfertilization across fragmented specialities of medicine and direct reintegration of Neuroscience, Neurology and Psychiatry into a continuum of medical sciences away from the silo approach. Precision medicine is biomarker-guided medicine on systems-levels that takes into account methodological advancements and discoveries of the comprehensive pathophysiological profiles of complex multi-factorial neurodegenerative diseases, such as late-onset sporadic AD. This will allow identifying and characterizing the disease processes at the asymptomatic preclinical stage, where pathophysiological and topographical abnormalities precede overt clinical symptoms by many years to decades. In this respect, the uncharted territory of the AD preclinical stage has become a major research challenge as the field postulates that early biomarker guided customized interventions may offer the best chance of therapeutic success. Clarification and practical operationalization is needed for comprehensive dissection and classification of interacting and converging disease mechanisms, description of genomic and epigenetic drivers, natural history trajectories through space and time, surrogate biomarkers and indicators of risk and progression, as well as considerations about the regulatory, ethical, political and societal consequences of early detection at asymptomatic stages. In this scenario, the integrated roles of genome sequencing, investigations of comprehensive fluid-based biomarkers and multimodal neuroimaging will be of key importance for the identification of distinct molecular mechanisms and signaling pathways in subsets of asymptomatic people at greatest risk for progression to clinical milestones due to those specific pathways. The precision medicine strategy facilitates a paradigm shift in Neuroscience and AD research and development away from the classical “one-size-fits-all” approach in drug discovery towards biomarker guided “molecularly” tailored therapy for truly effective treatment and prevention options. After the long and winding decade of failed therapy trials progress towards the holistic systems-based strategy of precision medicine may finally turn into the new age of scientific and medical success curbing the global AD epidemic.

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MicroRNA deregulation and chemotaxis and phagocytosis impairment in Alzheimer's disease

Cited by 60 publications

References 50 publications

Profile of 6 microRNA in blood plasma distinguish early stage Alzheimer’s disease patients from non-demented subjects

Profile of 6 microRNA in blood plasma distinguish early stage Alzheimer’s disease patients from non-demented subjects

Higher Peripheral TREM2 mRNA Levels Relate to Cognitive Deficits and Hippocampal Atrophy in Alzheimer’s Disease and Amnestic Mild Cognitive Impairment

Precision Medicine - The Golden Gate for Detection, Treatment and Prevention of Alzheimer’s Disease

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