Association of AEBP1 and NRN1 RNA expression with Alzheimer’s disease and neurofibrillary tangle density in middle temporal gyrus
| Autor: | Ignazio S. Piras, Jonida Krate, Diego Mastroeni, Matthew De Both, Matthew J. Huentelman, Jennifer Nolz, Geidy E. Serrano, Elaine Delvaux, Lucia I. Sue, Thomas G. Beach, Paul D. Coleman |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Middle temporal gyrus Gene Expression Hippocampus tau Proteins Carboxypeptidases Biology GPI-Linked Proteins Transcriptome 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Alzheimer Disease Gene expression medicine Humans Cognitive Dysfunction Molecular Biology Aged Aged 80 and over General Neuroscience Neuropeptides Brain RNA Neurofibrillary Tangles Neurofibrillary tangle medicine.disease Temporal Lobe Repressor Proteins 030104 developmental biology Female Neurology (clinical) Neuroscience 030217 neurology & neurosurgery Braak staging Developmental Biology |
| Zdroj: | Brain Research. 1719:217-224 |
| ISSN: | 0006-8993 |
| Popis: | We explored RNA expression changes in the middle temporal gyrus (MTG) of Alzheimer's Disease patients (AD) by RNA sequencing the whole transcriptome of 8 AD and 8 Non-Demented (ND) controls. We used three additional expression datasets from related brain regions to validate the findings. The results highlighted the upregulation of AEBP1 and downregulation of NRN1 in AD, as well as their association with Braak staging and neurofibrillary tangles density. Furthermore, more than 400 protein-coding RNAs enriched for "Clathrin-mediated endocytosis" were validated in independent datasets from the same brain region. Finally, using in silico prediction analysis we found a signature of 52 non-protein coding RNAs that perturb key pathways involved in GABAergic transmission and peptide chain elongation. The association of AEBP1 in our data confirmed other published work examining gene expression in the hippocampus of AD patients. NRN1 is involved in neurite outgrowth, and in previous studies it has been shown to reverse synaptic defects and cognitive function impairment in Tg2576 mice. Finally, our results on non-protein coding RNAs suggest a role of these transcripts in altering synaptic and amyloid-β associated pathways. |
| Databáze: | OpenAIRE |
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