Identification of miRNAs regulating MAPT expression and their analysis in plasma of patients with dementia
Paola PiscopoMargherita GrassoValeria ManziniAndrea ZeniMichele CastelluzzoFrancesca FontanaGiuseppina TalaricoAnna Elisa CastellanoRoberto RivabeneAlessio CrestiniGiuseppe BrunoLeonardo RicciMichela A. Denti
5
Citation
50
Reference
10
Related Paper
Citation Trend
Abstract:
Dementia is one of the most common diseases in elderly people and hundreds of thousand new cases per year of Alzheimer's disease (AD) are estimated. While the recent decade has seen significant advances in the development of novel biomarkers to identify dementias at their early stage, a great effort has been recently made to identify biomarkers able to improve differential diagnosis. However, only few potential candidates, mainly detectable in cerebrospinal fluid (CSF), have been described so far.We searched for miRNAs regulating MAPT translation. We employed a capture technology able to find the miRNAs directly bound to the MAPT transcript in cell lines. Afterwards, we evaluated the levels of these miRNAs in plasma samples from FTD (n = 42) and AD patients (n = 33) and relative healthy controls (HCs) (n = 42) by using qRT-PCR.Firstly, we found all miRNAs that interact with the MAPT transcript. Ten miRNAs have been selected to verify their effect on Tau levels increasing or reducing miRNA levels by using cell transfections with plasmids expressing the miRNAs genes or LNA antagomiRs. Following the results obtained, miR-92a-3p, miR-320a and miR-320b were selected to analyse their levels in plasma samples of patients with FTD and AD respect to HCs. The analysis showed that the miR-92a-1-3p was under-expressed in both AD and FTD compared to HCs. Moreover, miR-320a was upregulated in FTD vs. AD patients, particularly in men when we stratified by sex. Respect to HC, the only difference is showed in men with AD who have reduced levels of this miRNA. Instead, miR-320b is up-regulated in both dementias, but only patients with FTD maintain this trend in both genders.Our results seem to identify miR-92a-3p and miR-320a as possible good biomarkers to discriminate AD from HC, while miR-320b to discriminate FTD from HC, particularly in males. Combining three miRNAs improves the accuracy only in females, particularly for differential diagnosis (FTD vs. AD) and to distinguish FTD from HC.Keywords:
Frontotemporal lobar degeneration
Frontotemporal lobar degeneration
Semantic dementia
Nosology
Corticobasal degeneration
Neuropsychiatry
Cite
Citations (157)
Frontotemporal lobar degeneration
Executive dysfunction
Cite
Citations (131)
Frontotemporal lobar degeneration
Degeneration (medical)
Presentation (obstetrics)
Pick's disease
Dysarthria
Cite
Citations (6)
Frontotemporal lobar degenerations are clinically, genetically, and molecularly heterogeneous diseases characterized by mainly frontal and temporal atrophy and affecting behavioral, language, cognitive, and motor functions. The term frontotemporal dementia incorporates 3 distinct clinical syndromes seen in frontotemporal degenerations: behavioral variant of frontotemporal dementia, progressive nonfluent aphasia, and semantic dementia. Progressive supranuclear palsy syndrome, corticobasal syndrome, and motor neuron disease syndrome are also associated with frontotemporal lobar degenerations. The neuropathologic hallmark of frontotemporal lobar degenerations is accumulation of abnormal proteins in the cytoplasm and nuclei of neurons and glial cells. Proteins involved in pathologic processes that represent the basis for frontotemporal lobar degeneration classification are tau protein, transactive response DNA-binding protein of 43 kDa, and "fused in sarcoma" protein. The aim of this review is to provide a summary of practical approaches for neuropathologic diagnostics of the rapidly evolving classifications of frontotemporal lobar degenerations.
Frontotemporal lobar degeneration
Semantic dementia
Corticobasal degeneration
Primary progressive aphasia
Cite
Citations (13)
Frontotemporal lobar degeneration
Semantic dementia
Primary progressive aphasia
Degeneration (medical)
Cite
Citations (5)
Frontotemporal dementia (FTD) is an uncommon but important form of degenerative disease characterized by clinical syndromes that result from degeneration of the frontal and temporal lobes. FTD is divided based on clinical presentation into behavioral variant FTD (bvFTD), semantic dementia, and progressive nonfluent/agrammatic aphasia. Several recent studies have advanced our knowledge of the genetics of FTD, with the three most common FTD genes being microtubule-associated protein tau (MAPT) and progranulin (GRN), and a noncoding repeat expansion in C9ORF72. Tau and TDP-43 are the most common pathologies associated with FTD. No pharmacological therapies are currently approved for use in FTD.
C9ORF72
Frontotemporal lobar degeneration
Semantic dementia
Primary progressive aphasia
Tauopathy
Corticobasal degeneration
Tau protein
Cite
Citations (1)
Frontotemporal lobar degeneration
Cite
Citations (0)
Research into the non-Alzheimer dementias has exploded over the last 2 decades, and frontotemporal lobar degeneration has emerged as the most common cause of dementia in patients below the age of 65. In 1998, an international consortium of investigators focusing on this disease entity met and agreed upon the classification of 3 subtypes of frontotemporal lobar degeneration, using regional atrophy to distinguish them. These are: a frontally predominant form called frontotemporal dementia, a temporally predominant form called semantic dementia, and a left-frontally predominant syndrome, called progressive nonfluent aphasia. With the rise of genetic and neuropathologic findings, however, the usefulness of this subtype classification has been called into question. This paper discusses the major pertinent findings, and the implications of classifying the disease on the basis of atrophy versus genetic or molecular mechanisms.
Semantic dementia
Frontotemporal lobar degeneration
Primary progressive aphasia
Cite
Citations (10)
Frontotemporal dementia is the second most common early onset dementia after Alzheimer disease. Frontotemporal dementias are a complex group of dementias. The clinical diagnosis can be perplexing because of concurring psychiatric and neurologic syndromes. Frontotemporal lobar degeneration, the underlying pathology, represents an emerging group of proteinopathies. Genetic factors play an important part in the etiologies of dementias. This article overviews current defining characteristics of frontotemporal dementias known also as frontotemporal lobar degenerations.
Frontotemporal lobar degeneration
Semantic dementia
Cite
Citations (5)
Frontotemporal lobar degeneration
C9ORF72
Cite
Citations (40)