Cited by 1,652Alzheimer's disease research and treatmentsPrion Diseases and Protein MisfoldingDementia and Cognitive Impairment Research

MODELS OF AMYLOID SEEDING IN ALZHEIMER'S DISEASE AND SCRAPIE: Mechanistic Truths and Physiological Consequences of the Time-Dependent Solubility of Amyloid Proteins

Harper, James D., Lansbury, Peter T.·1997·Annual Review of Biochemistry

Abstract

Ordered protein aggregation in the brain is a hallmark of Alzheimer's disease and scrapie. The disease-specific amyloid fibrils comprise primarily a single protein, amyloid beta, in Alzheimer's disease, and the prion protein in scrapie. These proteins can be induced to form aggregates in vitro that are indistinguishable from brain-derived fibrils. Consequently, much effort has been invested in the development of in vitro model systems to study the details of the aggregation processes and the effects of endogenous molecules that have been implicated in disease. Selected studies of this type are reviewed herein. A simple mechanistic model has emerged for both processes that involves a nucleation-dependent polymerization. This mechanism dictates that aggregation is dependent on protein concentration and time. Furthermore, amyloid formation can be seeded by a preformed fibril. The physiological consequences of this mechanism are discussed.

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Crossref · 10.1146/annurev.biochem.66.1.385

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  • Ongoing microglial phagocytosis around growing fibrillar deposits could reduce levels of oligomeric and protofibrillar Aβ, which may change the equilibrium between monomers, oligomers and fibrils, altering nucleation-dependent polymerization that leads to fibrillar plaque formation.

    “Ongoing microglial phagocytosis around growing fibrillar deposits could reduce levels of oligomeric and protofibrillar Aβ, which may change the equilibrium between monomers, oligomers and fibrils, altering the process of nucleation-dependent polymerization that leads to fibrillar plaque formation (Harper and Lansbury Jr., 1997; Walsh et al., 1999).”

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Authors
Harper, J. D., & Lansbury, P. T.
Affiliations
  • Massachusetts Institute of Technology (US)
  • Brigham and Women's Hospital (US)
Venue
Annual Review of Biochemistry
Published
1997-06
Volume
66
Issue
1
Pages
385-407
ISSN
  • 0066-4154 (ISSN-L)
  • 1545-4509
OpenAlex
W2096601751
Cited by
1,652
References
10
Citations by year
2026: 14 · 2025: 19 · 2024: 33 · 2023: 22 · 2022: 23 · 2021: 45 · 2020: 39 · 2019: 45 · 2018: 50 · 2017: 55 · 2016: 56 · 2015: 66 · 2014: 67 · 2013: 110 · 2012: 81
FWCI
4.92
Type
journal article
Language
en
Open access
closed
Locations
  • Annual Review of Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
amyloid seeding, Alzheimer's disease, scrapie, amyloid-beta, prion protein, protein aggregation, amyloid fibrils, prion propagation
MeSH terms
Alzheimer Disease, Amino Acid Sequence, Amyloid, Animals, Brain, Humans, Molecular Sequence Data, Scrapie, Solubility, Time Factors

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