Anti-tau oligomers passive vaccination for the treatment of Alzheimer disease

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The aggregation and accumulation of the microtubule-associated protein (tau) is a pathological hallmark of Alzheimer disease (AD) and many neurodegenerative diseases. Despite the poor correlation between neurofibrillary tangles (NFTs) and disease progression, and evidence showing that neuronal loss in AD actually precedes NFTs formation, research until recently focused on them and other large meta-stable inclusions composed of aggregated hyperphosphorylated tau protein. Lately, the significance and toxicity of NFTs have been challenged and a new aggregated tau entity has emerged as the true pathogenic species in tauopathies and a possible mediator of Aβ toxicity in AD. Tau intermediate aggregate (tau oligomers; aggregates of an intermediate that is between monomers and NFTs in size) can cause neurodegeneration and memory impairment in the absence of Aβ. This exciting body of evidence includes results from human brain samples, transgenic mouse and cell-based studies. Despite extensive efforts to develop a safe and efficacious vaccine for AD using Aβ peptide as an immunogen in active vaccination approaches or anti Aβ antibodies for passive vaccination, success has been modest. Nonetheless, these studies have produced a wealth of fundamental knowledge that has potential application to the development of a tau-based immunotherapy. Herein, I discuss the evidence supporting the critical role of tau oligomers in AD, the potential and challenges for targeting them by immunotherapy as a novel approach for AD treatment.

Original languageEnglish (US)
Pages (from-to)931-935
Number of pages5
JournalHuman Vaccines
Volume6
Issue number11
DOIs
StatePublished - Nov 2010

Fingerprint

Alzheimer Disease
Neurofibrillary Tangles
Vaccination
Immunotherapy
Therapeutics
Tauopathies
tau Proteins
Microtubule-Associated Proteins
Neurodegenerative Diseases
Transgenic Mice
Disease Progression
Anti-Idiotypic Antibodies
Vaccines
Peptides
Brain
Research

Keywords

  • Alzheimer disease
  • Immunotherapy
  • Neurodegeneration
  • Tau oligomers

ASJC Scopus subject areas

  • Immunology
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Anti-tau oligomers passive vaccination for the treatment of Alzheimer disease. / Kayed, Rakez.

In: Human Vaccines, Vol. 6, No. 11, 11.2010, p. 931-935.

Research output: Contribution to journalArticle

@article{d2e6f3936ecc4f0980a63938187d3005,
title = "Anti-tau oligomers passive vaccination for the treatment of Alzheimer disease",
abstract = "The aggregation and accumulation of the microtubule-associated protein (tau) is a pathological hallmark of Alzheimer disease (AD) and many neurodegenerative diseases. Despite the poor correlation between neurofibrillary tangles (NFTs) and disease progression, and evidence showing that neuronal loss in AD actually precedes NFTs formation, research until recently focused on them and other large meta-stable inclusions composed of aggregated hyperphosphorylated tau protein. Lately, the significance and toxicity of NFTs have been challenged and a new aggregated tau entity has emerged as the true pathogenic species in tauopathies and a possible mediator of Aβ toxicity in AD. Tau intermediate aggregate (tau oligomers; aggregates of an intermediate that is between monomers and NFTs in size) can cause neurodegeneration and memory impairment in the absence of Aβ. This exciting body of evidence includes results from human brain samples, transgenic mouse and cell-based studies. Despite extensive efforts to develop a safe and efficacious vaccine for AD using Aβ peptide as an immunogen in active vaccination approaches or anti Aβ antibodies for passive vaccination, success has been modest. Nonetheless, these studies have produced a wealth of fundamental knowledge that has potential application to the development of a tau-based immunotherapy. Herein, I discuss the evidence supporting the critical role of tau oligomers in AD, the potential and challenges for targeting them by immunotherapy as a novel approach for AD treatment.",
keywords = "Alzheimer disease, Immunotherapy, Neurodegeneration, Tau oligomers",
author = "Rakez Kayed",
year = "2010",
month = "11",
doi = "10.4161/hv.6.11.12689",
language = "English (US)",
volume = "6",
pages = "931--935",
journal = "Human Vaccines",
issn = "1554-8600",
publisher = "Landes Bioscience",
number = "11",

}

TY - JOUR

T1 - Anti-tau oligomers passive vaccination for the treatment of Alzheimer disease

AU - Kayed, Rakez

PY - 2010/11

Y1 - 2010/11

N2 - The aggregation and accumulation of the microtubule-associated protein (tau) is a pathological hallmark of Alzheimer disease (AD) and many neurodegenerative diseases. Despite the poor correlation between neurofibrillary tangles (NFTs) and disease progression, and evidence showing that neuronal loss in AD actually precedes NFTs formation, research until recently focused on them and other large meta-stable inclusions composed of aggregated hyperphosphorylated tau protein. Lately, the significance and toxicity of NFTs have been challenged and a new aggregated tau entity has emerged as the true pathogenic species in tauopathies and a possible mediator of Aβ toxicity in AD. Tau intermediate aggregate (tau oligomers; aggregates of an intermediate that is between monomers and NFTs in size) can cause neurodegeneration and memory impairment in the absence of Aβ. This exciting body of evidence includes results from human brain samples, transgenic mouse and cell-based studies. Despite extensive efforts to develop a safe and efficacious vaccine for AD using Aβ peptide as an immunogen in active vaccination approaches or anti Aβ antibodies for passive vaccination, success has been modest. Nonetheless, these studies have produced a wealth of fundamental knowledge that has potential application to the development of a tau-based immunotherapy. Herein, I discuss the evidence supporting the critical role of tau oligomers in AD, the potential and challenges for targeting them by immunotherapy as a novel approach for AD treatment.

AB - The aggregation and accumulation of the microtubule-associated protein (tau) is a pathological hallmark of Alzheimer disease (AD) and many neurodegenerative diseases. Despite the poor correlation between neurofibrillary tangles (NFTs) and disease progression, and evidence showing that neuronal loss in AD actually precedes NFTs formation, research until recently focused on them and other large meta-stable inclusions composed of aggregated hyperphosphorylated tau protein. Lately, the significance and toxicity of NFTs have been challenged and a new aggregated tau entity has emerged as the true pathogenic species in tauopathies and a possible mediator of Aβ toxicity in AD. Tau intermediate aggregate (tau oligomers; aggregates of an intermediate that is between monomers and NFTs in size) can cause neurodegeneration and memory impairment in the absence of Aβ. This exciting body of evidence includes results from human brain samples, transgenic mouse and cell-based studies. Despite extensive efforts to develop a safe and efficacious vaccine for AD using Aβ peptide as an immunogen in active vaccination approaches or anti Aβ antibodies for passive vaccination, success has been modest. Nonetheless, these studies have produced a wealth of fundamental knowledge that has potential application to the development of a tau-based immunotherapy. Herein, I discuss the evidence supporting the critical role of tau oligomers in AD, the potential and challenges for targeting them by immunotherapy as a novel approach for AD treatment.

KW - Alzheimer disease

KW - Immunotherapy

KW - Neurodegeneration

KW - Tau oligomers

UR - http://www.scopus.com/inward/record.url?scp=78649360496&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649360496&partnerID=8YFLogxK

U2 - 10.4161/hv.6.11.12689

DO - 10.4161/hv.6.11.12689

M3 - Article

C2 - 20980799

AN - SCOPUS:78649360496

VL - 6

SP - 931

EP - 935

JO - Human Vaccines

JF - Human Vaccines

SN - 1554-8600

IS - 11

ER -