Identification of an amino-terminal fragment of apolipoprotein E4 that localizes to neurofibrillary tangles of the Alzheimer's disease brain
| Autor: | Jeffrey W. Habig, Kendra G. Coonse, Lindsey W. Catlin, Troy T. Rohn |
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| Rok vydání: | 2012 |
| Předmět: |
Gene isoform
Proteolysis Apolipoprotein E4 Molecular Sequence Data Cleavage (embryo) law.invention Tangle Pathogenesis Western blot law Alzheimer Disease mental disorders medicine Humans Amino Acid Sequence Molecular Biology medicine.diagnostic_test biology Chemistry General Neuroscience Brain Neurofibrillary Tangles Molecular biology Peptide Fragments Biochemistry Recombinant DNA biology.protein lipids (amino acids peptides and proteins) Neurology (clinical) Antibody human activities Developmental Biology |
| Zdroj: | Brain research. 1475 |
| ISSN: | 1872-6240 |
| Popis: | Although the risk factor for harboring the apolipoprotein E4 (apoE4) allele in late-onset Alzheimer's disease (AD) is well known, the mechanism by which apoE4 contributes to AD pathogenesis has yet to be clarified. Preferential cleavage of the ApoE4 isoform relative to other polymorphic forms appears to be significant, as the resulting fragments are associated with hallmarks of AD. To examine the possible role of apoE4 proteolysis in AD, we designed a site-directed antibody directed at position D172, which would yield a predicted amino-terminal fragment previously identified in AD brain extracts. Western blot analysis utilizing this novel antibody, termed the amino-terminal apoE4 cleavage fragment (nApoE4CF) Ab, consistently identified the predicted amino-terminal fragment (∼18 kDa) in several commercially available forms of human recombinant apoE4 purified from E. coli . Mass spectrometry confirmed the identity of this 18 kDa fragment as being an amino-terminal fragment of apoE4. Immunohistochemical experiments indicated the nApoE4CF Ab specifically labeled neurofibrillary tangles (NFTs) in AD frontal cortex sections that colocalized with the mature tangle marker PHF-1. Taken together, these results suggest a novel cleavage event of apoE4, generating an amino-terminal fragment that localizes within NFTs of the AD brain. |
| Databáze: | OpenAIRE |
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