Bridging integrator 1 (BIN1) protein expression increases in the Alzheimer's disease brain and correlates with neurofibrillary tangle pathology
| Autor: | Elizabeth Head, Christopher J. Holler, Robin L. Webb, Thomas L. Platt, Paulina R. Davis, Tina L. Beckett, M. Paul Murphy |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Pathology Aging Hippocampus Plaque Amyloid Genome-wide association study Neurodegenerative Alzheimer's Disease Cortex (anatomy) 80 and over 2.1 Biological and endogenous factors Senile plaques tau Aetiology Plaque Aged 80 and over Tumor Blotting General Neuroscience Brain Adaptor Proteins Nuclear Proteins Neurofibrillary Tangles General Medicine cellular nucleic acid binding protein Immunohistochemistry Psychiatry and Mental health Clinical Psychology medicine.anatomical_structure Neurological Electrophoresis Polyacrylamide Gel Female Cognitive Sciences Western Gene isoform Electrophoresis medicine.medical_specialty Amyloid Blotting Western Clinical Sciences tau Proteins Biology ZNF9 Myotonic dystrophy amyloid-β peptide Article Cell Line Isomerism Alzheimer Disease Cell Line Tumor medicine Acquired Cognitive Impairment Humans Adaptor Proteins Signal Transducing Aged Polyacrylamide Gel Amyloid beta-Peptides myotonic dystrophy Neurology & Neurosurgery Tumor Suppressor Proteins Signal Transducing Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Neurofibrillary tangle medicine.disease Axon initial segment Brain Disorders Dementia Geriatrics and Gerontology Neuroscience |
| Zdroj: | Journal of Alzheimer's disease : JAD, vol 42, iss 4 |
| Popis: | Recent genome wide association studies (GWAS) have implicated bridging integrator 1 (BIN1) as a late-onset Alzheimer’s disease (AD) susceptibility gene. There are at least 15 different known isoforms of BIN1, with many being expressed in the brain including the longest isoform (iso1), which is brain-specific and localizes to axon initial segments and nodes of Ranvier. It is currently unknown what role BIN1 plays in AD. We analyzed BIN1 protein expression from a large number (N = 71) of AD cases and controls from five different brain regions [hippocampus, inferior parietal (IP) cortex, inferior temporal (IT) cortex, frontal cortex (BA9), and superior and middle temporal gyri (SMTG)]. We found that the amount of the largest isoform of BIN1 was significantly reduced in the AD brain compared to age-matched controls, and smaller BIN1 isoforms were significantly increased. Further, BIN1 was significantly correlated with the amount of neurofibrillary tangle (NFT) pathology but not with either diffuse or neuritic plaques, or with the amount of amyloid-β peptide. BIN1 is known to be abnormally expressed in another human disease, myotonic dystrophy, which also features prominent NFT pathology. These data suggest that BIN1 is likely involved in AD as a modulator of NFT pathology, and that this role may extend to other human diseases that feature tau pathology. |
| Databáze: | OpenAIRE |
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