Abstract
Apolipoprotein E (APOE) genetic variation and aging are the two most noted risk factors associated with the development of Alzheimer’s disease (AD) related dementia. However, the relationship between these two pathological factors is not understood. Formaldehyde (FA) is an age related factor that has been found to be elevated in AD patients and is known to have protein cross-linking properties. FA forms cross-links with larger arginine, lysine and tryptophan residues but also has thiol reactivity. This study investigated the formation of protein aggregates between amyloid-beta (1-40) peptide (Aβ), the main component of amyloid plaques in AD, with APOE isoforms in vitro. APOE4 protein, the isoform with arginines at residue 112 and 158, was found to form aggregates with more Aβ (P < 0.001) and APOE (P < 0.05) protein content in 10 mM FA than aggregates formed with either APOE3 or APOE2 protein. This aggregation pattern reflected the trend of vulnerability conferred by the APOE genetic variation (APOE4 > APOE3 > APOE2) and suggested that FA may have a role in the differential pattern of amyloid plaque formation in people with differing APOE genetic backgrounds. All told, this finding adds to a growing body of evidence that FA has a role in AD progression as well as provides a novel link between aging and APOE risk factors; the cornerstones of one of the world’s largest mental health concerns.
Keywords: Aggregation, Alzheimer's disease, amyloid-beta, apolipoprotein E isoforms, formaldehyde, plaque formation.
Current Alzheimer Research
Title:Is Formaldehyde the Missing Link in AD Pathology? The Differential Aggregation of Amyloid-Beta with APOE Isoforms In Vitro
Volume: 11 Issue: 5
Author(s): Joshua D. Rizak, Yuanye Ma and Xintian Hu
Affiliation:
Keywords: Aggregation, Alzheimer's disease, amyloid-beta, apolipoprotein E isoforms, formaldehyde, plaque formation.
Abstract: Apolipoprotein E (APOE) genetic variation and aging are the two most noted risk factors associated with the development of Alzheimer’s disease (AD) related dementia. However, the relationship between these two pathological factors is not understood. Formaldehyde (FA) is an age related factor that has been found to be elevated in AD patients and is known to have protein cross-linking properties. FA forms cross-links with larger arginine, lysine and tryptophan residues but also has thiol reactivity. This study investigated the formation of protein aggregates between amyloid-beta (1-40) peptide (Aβ), the main component of amyloid plaques in AD, with APOE isoforms in vitro. APOE4 protein, the isoform with arginines at residue 112 and 158, was found to form aggregates with more Aβ (P < 0.001) and APOE (P < 0.05) protein content in 10 mM FA than aggregates formed with either APOE3 or APOE2 protein. This aggregation pattern reflected the trend of vulnerability conferred by the APOE genetic variation (APOE4 > APOE3 > APOE2) and suggested that FA may have a role in the differential pattern of amyloid plaque formation in people with differing APOE genetic backgrounds. All told, this finding adds to a growing body of evidence that FA has a role in AD progression as well as provides a novel link between aging and APOE risk factors; the cornerstones of one of the world’s largest mental health concerns.
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Cite this article as:
Rizak D. Joshua, Ma Yuanye and Hu Xintian, Is Formaldehyde the Missing Link in AD Pathology? The Differential Aggregation of Amyloid-Beta with APOE Isoforms In Vitro, Current Alzheimer Research 2014; 11 (5) . https://dx.doi.org/10.2174/1567205011666140425112043
DOI https://dx.doi.org/10.2174/1567205011666140425112043 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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