Water-soluble Aβ(N-40, N-42) oligomers in normal and Alzheimer disease brains

Kuo, Yu-Min; Emmerling, Mark R.; Vigo-Pelfrey, Carmen; Kasunic, Timothy C.; Kirkpatrick, Joel B.; Murdoch, Geoffrey H.; Ball, Melvyn J.; Roher, Alex E.

doi:10.1074/jbc.271.8.4077

Cited by 618Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Water-soluble Aβ(N-40, N-42) oligomers in normal and Alzheimer disease brains

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Kuo, Yu-Min, Emmerling, Mark R., Vigo-Pelfrey, Carmen, Kasunic, Timothy C., Kirkpatrick, Joel B., Murdoch, Geoffrey H., Ball, Melvyn J., Roher, Alex E.·1996·Journal of Biological Chemistry

DOI 10.1074/jbc.271.8.4077

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Abstract

Ultracentrifugation and graded molecular sieving, as well as a sensitive sandwich enzyme-linked immunosorbent assay were used to isolate and quantitate the amounts of water-soluble oligomers of beta amyloid (Abeta) peptides N-40 and N-42 in cerebral cortex of normal and Alzheimer disease (AD) brains. AD brains contained 6-fold more water-soluble Abeta (wsAbeta) than control brains. The majority of water-soluble peptides in most AD cases was A beta N-42, representing 12 times the amount found in control brains. The wsAbeta was present in the form of monomers and oligomers ranging from less than 10 kDa to greater than 100 kDa. The amount of wsAbeta N-42 in AD brains is about 50 times greater than the level of soluble Abeta N-42 found in the CSF of AD patients. This disparity may be due to the rapid association of wsAbeta N-42 into fibrillar deposits and/or to the integrity of the anatomical barriers which separate the two extracellular spaces. In this paper, we consider soluble any form of Abeta which has not yet polymerized into its insoluble, filamentous form. This includes both the newly synthesized forms of Abeta and those peptides which may be loosely attached to insoluble filaments but which can, nevertheless, still be considered soluble. It has been previously shown that, once it has aggregated into its filamentous form, the Abeta peptides are resistant to disaggregation and degradation by a number of denaturing agents and aqueous buffers containing proteolytic enzymes. Therefore, it is likely that the water-soluble Abeta peptides we quantified are precursors to its insoluble, filamentous form. Consequently, reducing the levels of soluble Abeta in AD brains could have profound effects on AD pathophysiology.

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The soluble fraction appears to contain A␤ oligomers in size ranges >100 kd, 30 to 100 kd, 10 to 30 kd, and <10 kd, corresponding to assemblies of >22 molecules, 7 to 22 molecules, 3 to 7 molecules, and monomers/dimers.
“By ultrafiltration and molecular sieving the soluble fraction appears to contain A␤ oligomers that fall within the following size ranges: Ͼ100 kd, 30 to 100 kd, 10 to 30 kd, and Ͻ10 kd, corresponding to assemblies of Ͼ22 molecules, 7 to 22 molecules, 3 to 7 molecules, and monomers/dimers.15”
From Soluble Amyloid β Peptide Concentration as a Predictor of Synaptic Change in Alzheimer's Disease (1999) · cites this paper as [15]

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Authors: Kuo, Y.-M., Emmerling, M. R., Vigo-Pelfrey, C., Kasunic, T. C., Kirkpatrick, J. B., Murdoch, G. H., Ball, M. J., & Roher, A. E.
Affiliations: Wayne State University (US)
Baylor College of Medicine (US)
Oregon Health & Science University (US)
Corresponding author: Roher, Alex E.
ORCID: Kuo, Yu-Min
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1996-02
Volume: 271
Issue: 8
Pages: 4077-4081
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.271.8.4077
OpenAlex: W1999206064
Cited by: 618
References: 26
Citations by year: 2026: 5 · 2025: 7 · 2024: 7 · 2023: 16 · 2022: 10 · 2021: 5 · 2020: 16 · 2019: 14 · 2018: 16 · 2017: 15 · 2016: 21 · 2015: 21 · 2014: 22 · 2013: 23 · 2012: 34
FWCI: 11.71
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 9050 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Institutes of Health (5p50ag008664-09, 5r01ag011925-05)
National Institute on Aging (AG-11925, 5P50AG-08664, P30 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: amyloid oligomers, Alzheimer's disease, cerebral cortex, amyloid fibril formation, cerebrospinal fluid amyloid, amyloid precursor protein, amyloid fibrils
MeSH terms: Adult, Aged, Aged, 80 and over, Alzheimer Disease, Cerebral Cortex, Chromatography, High Pressure Liquid, Dialysis, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Molecular Weight, Solubility, Ultracentrifugation, Ultrafiltration, Amyloid beta-Peptides, Macromolecular Substances

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Water-soluble Aβ(N-40, N-42) oligomers in normal and Alzheimer disease brains

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