Dataset Information

Altered Regulation of KIAA0566, and Katanin Signaling Expression in the Locus Coeruleus With Neurofibrillary Tangle Pathology.

ABSTRACT: The locus coeruleus (LC), which contains the largest group of noradrenergic neurons in the central nervous system innervating the telencephalon, is an early and constantly vulnerable region to neurofibrillary tangle (NFT) pathology in aging and Alzheimer's disease (AD). The present study using whole genome bisulfite sequencing and Infinium Human Methylation 450 BeadChip was designed to learn about DNA methylation profiles in LC with age and NFT pathology. This method identified decreased DNA methylation of Katanin-Interacting Protein gene (KIAA0566) linked to age and presence of NFT pathology. KIAA0566 mRNA expression demonstrated with RT-qPCR significantly decreased in cases with NFT pathology. Importantly, KIAA0566 immunoreactivity was significantly decreased only in LC neurons with NFTs, but not in neurons without tau pathology when compared with neurons of middle-aged individuals. These changes were accompanied by a similar pattern of selective p80-katanin reduced protein expression in neurons with NFTs. In contrast, p60-katanin subunit expression levels in the neuropil were similar in MA cases and cases with NFT pathology. Since katanin is a major microtubule-severing protein and KIAA0566 binds and interacts with katanin, de-regulation of the katanin-signaling pathway may have implications in the regulation of microtubule homeostasis in LC neurons with NFTs, thereby potentially interfering with maintenance of the cytoskeleton and transport.

SUBMITTER: Andres-Benito P

PROVIDER: S-EPMC5966574 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Altered Regulation of KIAA0566, and Katanin Signaling Expression in the Locus Coeruleus With Neurofibrillary Tangle Pathology.

Andrés-Benito Pol P Delgado-Morales Raul R Ferrer Isidro I

Frontiers in cellular neuroscience 20180517

The locus coeruleus (LC), which contains the largest group of noradrenergic neurons in the central nervous system innervating the telencephalon, is an early and constantly vulnerable region to neurofibrillary tangle (NFT) pathology in aging and Alzheimer's disease (AD). The present study using whole genome bisulfite sequencing and Infinium Human Methylation 450 BeadChip was designed to learn about DNA methylation profiles in LC with age and NFT pathology. This method identified decreased DNA met ...[more]

PMID: 29867364

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Project description:Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tangles and widespread neuronal loss in the brain. In recent years, blood biomarkers have emerged as a realistic prospect to highlight accumulating pathology for secondary prevention trials. Neurofilament light chain (NfL), a marker of axonal degeneration, is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. A strong relationship with cerebrospinal fluid (CSF) NfL suggests that these biomarker modalities reflect the same pathological process. Yet, the connection between blood NfL and brain tissue pathology has not been directly compared. In this study, longitudinal plasma NfL from cognitively healthy controls (n = 12) and AD participants (n = 57) were quantified by the Simoa platform. On reaching post-mortem, neuropathological assessment was performed on all participants, with additional frozen and paraffin-embedded tissue acquired from 26 participants for further biochemical (Aβ1-42, Aβ1-40, tau) and histological (NfL) evaluation. Plasma NfL concentrations were significantly increased in AD and correlated with cognitive decline, independent of age. Retrospective stratification based on Braak staging revealed that baseline plasma NfL concentrations were associated with higher neurofibrillary tangle pathology at post-mortem. Longitudinal increases in plasma NfL were observed in all Braak groupings; a significant negative association, however, was found between plasma NfL at time point 1 and both its rate of change and annual percentage increase. Immunohistochemical evaluation of NfL in the medial temporal gyrus (MTG) demonstrated an inverse relationship between Braak stages and NfL staining. Importantly, a significant negative correlation was found between the plasma NfL measurement closest to death and the level of NfL staining in the MTG at post-mortem. For the first time, we demonstrate that plasma NfL associates with the severity of neurofibrillary tangle pathology and neurodegeneration in the post-mortem brain.

Dataset Information

Altered Regulation of KIAA0566, and Katanin Signaling Expression in the Locus Coeruleus With Neurofibrillary Tangle Pathology.

Publications

Altered Regulation of KIAA0566, and Katanin Signaling Expression in the Locus Coeruleus With Neurofibrillary Tangle Pathology.

Similar Datasets

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