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NeuroMolecular Medicine

, Volume 4, Issue 1–2, pp 49–58 | Cite as

Interactions of amyloidogenic proteins

  • Benoit I. Giasson
  • Virginia M. Y. Lee
  • John Q. TrojanowskiEmail author
Article

Abstract

The various protein deposits of brain amyloidosis share common ultrastructural, biophysical, and histological properties. These amyloidogenic deposits can be composed of distinct proteins, which are conceptually associated with different neurodegenerative diseases. Amyloidogenic proteins are typically soluble monomeric precursors, which undergo remarkable conformation changes associated with the polymerization into 8− to 10−nm wide fibrils, which culminate in the formation of amyloid aggregates. Some amyloidogenic inclusions are extracellular, such as senile plaques of Alzheimer’s disease, which are composed of amyloid β (Aβ) peptides. However, intracytoplasmic amyloid aggregates, such as neurofibrillary tangles in Alzheimer’s disease and Lewy bodies in Parkinson’s disease, are composed of the proteins tau and α-synuclein, respectively. The mounting awareness that the latter proteins are directly linked to the etiology of spectrum of neurodegenerative diseases has resulted in the coining of the terms “tauopathies” and “synucleinopathies.” However, emerging evidence for the overlap in the pathological and clinical features of patients with brain amyloidosis suggests that they may be linked mechanistically. Recently, it was demonstrated that α-synuclein, which has the ability to readily form amyloid in vitro without the need of other co-factors, can initiate tau amyloid formation. Following this initiation step, α-synuclein and tau can synergize the polymerization of each other. Furthermore, increased levels of Aβ peptides in brain can promote the formation of intracellular tau and α-synuclein amyloid aggregates, although the mechanism for this process is still unclear. These results indicate that the formation of amyloid composed of different proteins can affect each other directly or indirectly, likely contributing to the overlap in clinical and pathological features.

Index Entries

Aβ peptide Alzheimer’s disease amyloid Parkinson’s disease synuclein tau 

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Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  • Benoit I. Giasson
    • 1
  • Virginia M. Y. Lee
    • 1
    • 2
  • John Q. Trojanowski
    • 1
    • 2
    Email author
  1. 1.Department of Pathology and Laboratory MedicineCenter for Neurodegenerative Disease ResearchPhiladelphia
  2. 2.Institute on Aging of the University of PennsylvaniaPhiladelphia

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