Chemical characterization of A beta 17-42 peptide, a component of diffuse amyloid deposits of Alzheimer disease
Open accessAbstract
A peptide corresponding to the amino acid sequence of A beta 17-42 (LVFFAEDVGSNKGAIIGLMVGGVVIA) was isolated from Alzheimer Disease patient brains containing large deposits of diffuse-type amyloid. Brain homogenates were lysed in SDS and submitted to high speed centrifugations. A beta peptides were purified by size exclusion chromatography on Superose 12 and TSK 3000 SW columns. An A beta peptide with M(r) of 3,000 was recovered that on automatic gas-phase Edman degradation yielded the amino acid sequence of A beta starting at residue 17 (Leu). The 3-kDa peptide was subsequently hydrolyzed with trypsin and reacted with CNBr, and the resulting peptides were separated by reverse phase high pressure liquid chromatography and characterized by amino acid analyses, peptide microsequencing, and mass spectrometry. Hydrolysis of beta-amyloid precursor protein 695 at Lys612-Leu613 or at Lys16-Leu17 of its A beta 1-42 derivative prevents the generation of neurotoxic A beta filaments, thus leading to the formation of A beta 17-42 localized in the diffuse amyloid deposits. An outstanding feature in the pathology of Alzheimer Disease is that the predominant A beta peptides have their C termini at position 42, whether in the cores of the neuritic plaques, in the vascular walls, or in the diffuse deposits. Based on these observations, we postulate that the accumulation of insoluble A beta N-42 in Alzheimer Disease is due to the anomalous processing of the C-terminal region.
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This finding is consistent with previous reports that most of the Aβ in AD brains is amino-terminally truncated or modified.
“Th is finding is consistent with pr evious re ports (15,17,18) that most of the A{3 in AD brains is amino-ter mi na lly trunca te d or modifi ed.”
From Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain (1995) · cites this paper as [18]
The increased amount of Aβ detected with 4G8 suggests that there may be considerable amino-terminally truncated Aβ in AD brain.
“The increased amount of A{3 detected with 4G8 suggests that there may be considerable amino-terminally truncated A{3 in AD brain, consistent with the results of others who have examined the SDSinsoluble A{3 in AD brain (1S, 17,18).”
From Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain (1995) · cites this paper as [18]
Diffuse plaques are primarily Aβ17-42.
“that diffuse plaques are primarily A{317-42 (18)”
From Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain (1995) · cites this paper as [18]
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- Authors
- Gowing, E., Roher, A. E., Woods, A. S., Cotter, R. J., Chaney, M., Little, S. P., & Ball, M. J.
- Affiliations
- Wayne State University (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1994-04
- Volume
- 269
- Issue
- 15
- Pages
- 10987-10990
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1531666134
- Cited by
- 223
- References
- 4
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 9 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 9 · 2015: 2 · 2014: 7 · 2013: 6 · 2012: 4
- FWCI
- 11.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG 08017, P30AG008017)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, C-terminal processing, peptide purification, neuritic plaques, brain amyloid
- MeSH terms
- Alzheimer Disease, Amino Acid Sequence, Brain, Brain Chemistry, Chromatography, Gel, Chromatography, High Pressure Liquid, Frontal Lobe, Humans, Molecular Sequence Data, Peptide Fragments, Mass Spectrometry, Temporal Lobe, Amyloid beta-Peptides
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