Cited by 381Alzheimer's disease research and treatmentsProtein purification and stabilityDementia and Cognitive Impairment Research

Amyloid-beta aggregation: selective inhibition of aggregation in mixtures of amyloid with different chain lengths

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Snyder, S.W., Ladror, U.S., Wade, W.S., Wang, G.T., Barrett, L.W., Matayoshi, E.D., Huffaker, H.J., Krafft, G.A. +1 more·1994·Biophysical Journal

Abstract

One of the clinical manifestations of Alzheimer's disease is the deposition of the 39-43 residue amyloid-beta (A beta) peptide in aggregated fibrils in senile plaques. Characterization of the aggregation behavior of A beta is one of the critical issues in understanding the role of A beta in the disease process. Using solution hydrodynamics, A beta was observed to form three types of species in phosphate-buffered saline: insoluble aggregates with sedimentation coefficients of approximately 50,000 S and molecular masses of approximately 10(9) Da, "soluble aggregates" with sedimentation coefficients of approximately 30 S and masses of approximately 10(6) Da, and monomer. When starting from monomer, the aggregation kinetics of A beta 1-40 (A beta 40) and A beta 1-42 (A beta 42), alone and in combination, reveal large differences in the tendency of these peptides to aggregate as a function of pH and other solution conditions. At pH 4.1 and 7.0-7.4, aggregation is significantly slower than at pH 5 and 6. Under all conditions, aggregation of the longer A beta 42 was more rapid than A beta 40. Oxidation of Met-35 to the sulfoxide in A beta 40 enhances the aggregation rate over that of the nonoxidized peptide. Aggregation was found to be dependent upon temperature and to be strongly dependent on peptide concentration and ionic strength, indicating that aggregation is driven by a hydrophobic effect. When A beta 40 and A beta 42 are mixed together, A beta 40 retards the aggregation of A beta 42 in a concentration-dependent manner. Shorter fragments have a decreasing ability to interfere with A beta 42 aggregation. Conversely, the rate of aggregation of A beta 40 can be significantly enhanced by seeding slow aggregating solutions with preformed aggregates of A beta 42. Taken together, the inhibition of A beta 42 aggregation by A beta 40, the seeding of A beta 40 aggregation by A beta 42 aggregates, and the chemical oxidation of A beta 40 suggest that the relative abundance and rates of production of different-length A beta and its exposure to radical damage may be factors in the accumulation of A beta in plaques in vivo.

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  • The increased amyloid beta 42:40 ratio in oligodendrocytes could contribute to the high proportion of soluble aggregates.

    “The increased Aβ 42:40 ratio in oligodendrocytes could contribute to the high proportion of soluble aggregates [28,42,43]”

    From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [42]

    The discussion section (page not provided) speculates that the Aβ42:Aβ40 ratio affects how much amyloid accumulates, and the abstract identifies soluble aggregates among the species formed in solution. The paper does not study oligodendrocytes or show that a higher ratio increases the proportion of aggregates that are soluble. (LLM, conf=0.84)

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Research works printed but not linked: 4

  1. Gorevic, P. D., P. C. Munoz, T. T. Casey, C. R. Diraimondo, W. J. Stone, F. C. Prelli, M K Rodrigues, K D. Poulk, and B. Franikone. 1986. Ten to fourt residue pepqides of Alzheimer's disease protein are sufficient for amyloid fibril formaton and its characteristic x-ray dffraction pattern. Proc. Natl Acad Sci USA. 83:7908-7912.
  2. Holzman, T. F., and S. W. Snyder. 1994. Applicatons of analytical ultra- centrugation i sucture-bsed drug design. In Modern Analytical Ul- tracentifugation: Acquisition and Interpretation of Data for Biological and Synthetic Polymer Systems. T. M. Schuster, T. M. Laue, editors. Boston, Birkhauser Division, Springer-Verlag.
  3. Kirschner, D. A, C. R. Abraham, and D. J. Selkoe. 1986. X-ray diffractio from intraneuronal paired helical filaments and extraneuronal amyloid fibminAlzheimer disease indicates cross-beta conformation. Proc. NatiL Acad ScL U.S.A 86:503-507.
  4. Krafft, G. A. 1993. Perspectives on amyloid and Alzheimer's disease: a critical review. Annu. Rep. Mled Chem 28:49-58.

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Authors
Snyder, S. W., Ladror, U. S., Wade, W. S., Wang, G. T., Barrett, L. W., Matayoshi, E. D., Huffaker, H. J., Krafft, G. A., & Holzman, T. F.
Affiliations
Abbott (United Kingdom) (GB)
Corresponding author
Holzman, T.F.
Venue
Biophysical Journal
Publisher
Elsevier BV
Published
1994-09
Volume
67
Issue
3
Pages
1216-1228
ISSN
0006-3495 (ISSN-L)
OpenAlex
W2024559246
Cited by
381
References
55
Citations by year
2026: 4 · 2025: 2 · 2024: 17 · 2023: 5 · 2022: 9 · 2021: 20 · 2020: 8 · 2019: 12 · 2018: 9 · 2017: 18 · 2016: 13 · 2015: 9 · 2014: 10 · 2013: 18 · 2012: 17
FWCI
7.03
Type
journal article
Language
en
Open access
Locations
  • Biophysical Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Abbott Laboratories
  • National Institutes of Health (7p01ag010481-05)
  • National Institute on Aging (AG10481)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
amyloid-beta aggregation, Alzheimer's disease, Aβ40, amyloid-beta 42, peptide length, aggregation kinetics, hydrophobic effect, seeding, aggregation inhibition, pH dependence, ionic strength, amyloid plaques
MeSH terms
Alzheimer Disease, Amino Acid Sequence, Biophysics, Humans, Kinetics, Microscopy, Electron, Molecular Sequence Data, Polymers, Protein Conformation, Solutions, Amyloid beta-Peptides, Neurofibrillary Tangles, Macromolecular Substances, Biophysical Phenomena, In Vitro Techniques

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