The role of Aβ and tau oligomers in the pathogenesis of Alzheimer's disease

Kiran Bhaskar, Bruce Lamb

Research output: Chapter in Book/Report/Conference proceedingChapter

5 Citations (Scopus)

Abstract

Dense extracellular aggregates of amyloid β-protein (Aβ) in senile plaques (SPs) and intracellular aggregates of the hyperphosphorylated, microtubule-associated protein tau (MAPT) in neurofibrillary tangles (NFTs) within the brain are the key diagnostic hallmarks of Alzheimer's disease (AD). While initial studies focused on SPs and NFTs as the key pathogenic proteinaceous species that could account for the clinical features of AD, increasing evidence suggests that the fibrils of Aβ and MAPT are unlikely to be the unique neurotoxic entities responsible for AD pathogenesis. Instead, more recent studies have implicated small, soluble oligomeric species of both Aβ and MAPT. Indeed, a wide variety of Aβ and tau -oligomers have been described in both in vitro and in vivo systems that possess a diverse set of biological properties, including substantial synapto- and neurotoxicity. While many of these oligomers have been extensively characterized by novel biophysical, -biochemical, and immunological techniques, attributing particular functions and dysfunctions to particular oligomer structures in vivo has proven enormously difficult, as the different proteinaceous species are present in equilibrium and likely are contained within unique intracellular and extracellular environments. Nevertheless, a number of therapeutic strategies have been developed that seek to target Aβ and tau oligomerization for AD.

Original languageEnglish (US)
Title of host publicationNon-fibrillar Amyloidogenic Protein Assemblies - Common Cytotoxins Underlying Degenerative Diseases
PublisherSpringer Netherlands
Pages135-188
Number of pages54
Volume9789400727748
ISBN (Print)9789400727748, 9400727739, 9789400727731
DOIs
StatePublished - Mar 1 2012
Externally publishedYes

Fingerprint

Microtubule-Associated Proteins
Alzheimer Disease
Neurofibrillary Tangles
Amyloid Plaques
Immunologic Techniques
Serum Amyloid A Protein
Brain
Therapeutics

Keywords

  • Alzheimer's disease
  • Aβ oligomers
  • Neurofibrillary tangles
  • Neuropathology
  • Tau oligomers

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bhaskar, K., & Lamb, B. (2012). The role of Aβ and tau oligomers in the pathogenesis of Alzheimer's disease. In Non-fibrillar Amyloidogenic Protein Assemblies - Common Cytotoxins Underlying Degenerative Diseases (Vol. 9789400727748, pp. 135-188). Springer Netherlands. https://doi.org/10.1007/978-94-007-2774-8_5

The role of Aβ and tau oligomers in the pathogenesis of Alzheimer's disease. / Bhaskar, Kiran; Lamb, Bruce.

Non-fibrillar Amyloidogenic Protein Assemblies - Common Cytotoxins Underlying Degenerative Diseases. Vol. 9789400727748 Springer Netherlands, 2012. p. 135-188.

Research output: Chapter in Book/Report/Conference proceedingChapter

Bhaskar, K & Lamb, B 2012, The role of Aβ and tau oligomers in the pathogenesis of Alzheimer's disease. in Non-fibrillar Amyloidogenic Protein Assemblies - Common Cytotoxins Underlying Degenerative Diseases. vol. 9789400727748, Springer Netherlands, pp. 135-188. https://doi.org/10.1007/978-94-007-2774-8_5
Bhaskar K, Lamb B. The role of Aβ and tau oligomers in the pathogenesis of Alzheimer's disease. In Non-fibrillar Amyloidogenic Protein Assemblies - Common Cytotoxins Underlying Degenerative Diseases. Vol. 9789400727748. Springer Netherlands. 2012. p. 135-188 https://doi.org/10.1007/978-94-007-2774-8_5
Bhaskar, Kiran ; Lamb, Bruce. / The role of Aβ and tau oligomers in the pathogenesis of Alzheimer's disease. Non-fibrillar Amyloidogenic Protein Assemblies - Common Cytotoxins Underlying Degenerative Diseases. Vol. 9789400727748 Springer Netherlands, 2012. pp. 135-188
@inbook{eacbc50a62f34b1488cab7326222a06a,
title = "The role of Aβ and tau oligomers in the pathogenesis of Alzheimer's disease",
abstract = "Dense extracellular aggregates of amyloid β-protein (Aβ) in senile plaques (SPs) and intracellular aggregates of the hyperphosphorylated, microtubule-associated protein tau (MAPT) in neurofibrillary tangles (NFTs) within the brain are the key diagnostic hallmarks of Alzheimer's disease (AD). While initial studies focused on SPs and NFTs as the key pathogenic proteinaceous species that could account for the clinical features of AD, increasing evidence suggests that the fibrils of Aβ and MAPT are unlikely to be the unique neurotoxic entities responsible for AD pathogenesis. Instead, more recent studies have implicated small, soluble oligomeric species of both Aβ and MAPT. Indeed, a wide variety of Aβ and tau -oligomers have been described in both in vitro and in vivo systems that possess a diverse set of biological properties, including substantial synapto- and neurotoxicity. While many of these oligomers have been extensively characterized by novel biophysical, -biochemical, and immunological techniques, attributing particular functions and dysfunctions to particular oligomer structures in vivo has proven enormously difficult, as the different proteinaceous species are present in equilibrium and likely are contained within unique intracellular and extracellular environments. Nevertheless, a number of therapeutic strategies have been developed that seek to target Aβ and tau oligomerization for AD.",
keywords = "Alzheimer's disease, Aβ oligomers, Neurofibrillary tangles, Neuropathology, Tau oligomers",
author = "Kiran Bhaskar and Bruce Lamb",
year = "2012",
month = "3",
day = "1",
doi = "10.1007/978-94-007-2774-8_5",
language = "English (US)",
isbn = "9789400727748",
volume = "9789400727748",
pages = "135--188",
booktitle = "Non-fibrillar Amyloidogenic Protein Assemblies - Common Cytotoxins Underlying Degenerative Diseases",
publisher = "Springer Netherlands",

}

TY - CHAP

T1 - The role of Aβ and tau oligomers in the pathogenesis of Alzheimer's disease

AU - Bhaskar, Kiran

AU - Lamb, Bruce

PY - 2012/3/1

Y1 - 2012/3/1

N2 - Dense extracellular aggregates of amyloid β-protein (Aβ) in senile plaques (SPs) and intracellular aggregates of the hyperphosphorylated, microtubule-associated protein tau (MAPT) in neurofibrillary tangles (NFTs) within the brain are the key diagnostic hallmarks of Alzheimer's disease (AD). While initial studies focused on SPs and NFTs as the key pathogenic proteinaceous species that could account for the clinical features of AD, increasing evidence suggests that the fibrils of Aβ and MAPT are unlikely to be the unique neurotoxic entities responsible for AD pathogenesis. Instead, more recent studies have implicated small, soluble oligomeric species of both Aβ and MAPT. Indeed, a wide variety of Aβ and tau -oligomers have been described in both in vitro and in vivo systems that possess a diverse set of biological properties, including substantial synapto- and neurotoxicity. While many of these oligomers have been extensively characterized by novel biophysical, -biochemical, and immunological techniques, attributing particular functions and dysfunctions to particular oligomer structures in vivo has proven enormously difficult, as the different proteinaceous species are present in equilibrium and likely are contained within unique intracellular and extracellular environments. Nevertheless, a number of therapeutic strategies have been developed that seek to target Aβ and tau oligomerization for AD.

AB - Dense extracellular aggregates of amyloid β-protein (Aβ) in senile plaques (SPs) and intracellular aggregates of the hyperphosphorylated, microtubule-associated protein tau (MAPT) in neurofibrillary tangles (NFTs) within the brain are the key diagnostic hallmarks of Alzheimer's disease (AD). While initial studies focused on SPs and NFTs as the key pathogenic proteinaceous species that could account for the clinical features of AD, increasing evidence suggests that the fibrils of Aβ and MAPT are unlikely to be the unique neurotoxic entities responsible for AD pathogenesis. Instead, more recent studies have implicated small, soluble oligomeric species of both Aβ and MAPT. Indeed, a wide variety of Aβ and tau -oligomers have been described in both in vitro and in vivo systems that possess a diverse set of biological properties, including substantial synapto- and neurotoxicity. While many of these oligomers have been extensively characterized by novel biophysical, -biochemical, and immunological techniques, attributing particular functions and dysfunctions to particular oligomer structures in vivo has proven enormously difficult, as the different proteinaceous species are present in equilibrium and likely are contained within unique intracellular and extracellular environments. Nevertheless, a number of therapeutic strategies have been developed that seek to target Aβ and tau oligomerization for AD.

KW - Alzheimer's disease

KW - Aβ oligomers

KW - Neurofibrillary tangles

KW - Neuropathology

KW - Tau oligomers

UR - http://www.scopus.com/inward/record.url?scp=84878626491&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878626491&partnerID=8YFLogxK

U2 - 10.1007/978-94-007-2774-8_5

DO - 10.1007/978-94-007-2774-8_5

M3 - Chapter

SN - 9789400727748

SN - 9400727739

SN - 9789400727731

VL - 9789400727748

SP - 135

EP - 188

BT - Non-fibrillar Amyloidogenic Protein Assemblies - Common Cytotoxins Underlying Degenerative Diseases

PB - Springer Netherlands

ER -