Reduction of soluble Aβ and tau, but not soluble Aβ alone, ameliorates cognitive decline in transgenic mice with plaques and tangles

Salvatore Oddo, Vitaly Vasilevko, Antonella Caccamo, Masashi Kitazawa, David H. Cribbs, Frank M. LaFerla

Research output: Contribution to journalArticle

241 Citations (Scopus)

Abstract

Increasing evidence points to soluble assemblies of aggregating proteins as a major mediator of neuronal and synaptic dysfunction. In Alzheimer disease (AD), soluble amyloid-β (Aβ) appears to be a key factor in inducing synaptic and cognitive abnormalities. Here we report the novel finding that soluble tau also plays a role in the cognitive decline in the presence of concomitant Aβ pathology. We describe improved cognitive function following a reduction in both soluble Aβ and tau levels after active or passive immunization in advanced aged 3xTg-AD mice that contain both amyloid plaques and neurofibrillary tangles (NFTs). Notably, reducing soluble Aβ alone did not improve the cognitive phenotype in mice with plaques and NFTs. Our results show that Aβ immunotherapy reduces soluble tau and ameliorates behavioral deficit in old transgenic mice.

Original languageEnglish (US)
Pages (from-to)39413-39423
Number of pages11
JournalJournal of Biological Chemistry
Volume281
Issue number51
DOIs
StatePublished - Dec 22 2006
Externally publishedYes

Fingerprint

Neurofibrillary Tangles
Amyloid
Transgenic Mice
Alzheimer Disease
Immunization
Passive Immunization
Amyloid Plaques
Pathology
Immunotherapy
Cognition
Vaccination
Phenotype
Proteins
Cognitive Dysfunction

ASJC Scopus subject areas

  • Biochemistry

Cite this

Reduction of soluble Aβ and tau, but not soluble Aβ alone, ameliorates cognitive decline in transgenic mice with plaques and tangles. / Oddo, Salvatore; Vasilevko, Vitaly; Caccamo, Antonella; Kitazawa, Masashi; Cribbs, David H.; LaFerla, Frank M.

In: Journal of Biological Chemistry, Vol. 281, No. 51, 22.12.2006, p. 39413-39423.

Research output: Contribution to journalArticle

Oddo, Salvatore ; Vasilevko, Vitaly ; Caccamo, Antonella ; Kitazawa, Masashi ; Cribbs, David H. ; LaFerla, Frank M. / Reduction of soluble Aβ and tau, but not soluble Aβ alone, ameliorates cognitive decline in transgenic mice with plaques and tangles. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 51. pp. 39413-39423.
@article{7f705a5c6fdf46fabfc22e92de263180,
title = "Reduction of soluble Aβ and tau, but not soluble Aβ alone, ameliorates cognitive decline in transgenic mice with plaques and tangles",
abstract = "Increasing evidence points to soluble assemblies of aggregating proteins as a major mediator of neuronal and synaptic dysfunction. In Alzheimer disease (AD), soluble amyloid-β (Aβ) appears to be a key factor in inducing synaptic and cognitive abnormalities. Here we report the novel finding that soluble tau also plays a role in the cognitive decline in the presence of concomitant Aβ pathology. We describe improved cognitive function following a reduction in both soluble Aβ and tau levels after active or passive immunization in advanced aged 3xTg-AD mice that contain both amyloid plaques and neurofibrillary tangles (NFTs). Notably, reducing soluble Aβ alone did not improve the cognitive phenotype in mice with plaques and NFTs. Our results show that Aβ immunotherapy reduces soluble tau and ameliorates behavioral deficit in old transgenic mice.",
author = "Salvatore Oddo and Vitaly Vasilevko and Antonella Caccamo and Masashi Kitazawa and Cribbs, {David H.} and LaFerla, {Frank M.}",
year = "2006",
month = "12",
day = "22",
doi = "10.1074/jbc.M608485200",
language = "English (US)",
volume = "281",
pages = "39413--39423",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "51",

}

TY - JOUR

T1 - Reduction of soluble Aβ and tau, but not soluble Aβ alone, ameliorates cognitive decline in transgenic mice with plaques and tangles

AU - Oddo, Salvatore

AU - Vasilevko, Vitaly

AU - Caccamo, Antonella

AU - Kitazawa, Masashi

AU - Cribbs, David H.

AU - LaFerla, Frank M.

PY - 2006/12/22

Y1 - 2006/12/22

N2 - Increasing evidence points to soluble assemblies of aggregating proteins as a major mediator of neuronal and synaptic dysfunction. In Alzheimer disease (AD), soluble amyloid-β (Aβ) appears to be a key factor in inducing synaptic and cognitive abnormalities. Here we report the novel finding that soluble tau also plays a role in the cognitive decline in the presence of concomitant Aβ pathology. We describe improved cognitive function following a reduction in both soluble Aβ and tau levels after active or passive immunization in advanced aged 3xTg-AD mice that contain both amyloid plaques and neurofibrillary tangles (NFTs). Notably, reducing soluble Aβ alone did not improve the cognitive phenotype in mice with plaques and NFTs. Our results show that Aβ immunotherapy reduces soluble tau and ameliorates behavioral deficit in old transgenic mice.

AB - Increasing evidence points to soluble assemblies of aggregating proteins as a major mediator of neuronal and synaptic dysfunction. In Alzheimer disease (AD), soluble amyloid-β (Aβ) appears to be a key factor in inducing synaptic and cognitive abnormalities. Here we report the novel finding that soluble tau also plays a role in the cognitive decline in the presence of concomitant Aβ pathology. We describe improved cognitive function following a reduction in both soluble Aβ and tau levels after active or passive immunization in advanced aged 3xTg-AD mice that contain both amyloid plaques and neurofibrillary tangles (NFTs). Notably, reducing soluble Aβ alone did not improve the cognitive phenotype in mice with plaques and NFTs. Our results show that Aβ immunotherapy reduces soluble tau and ameliorates behavioral deficit in old transgenic mice.

UR - http://www.scopus.com/inward/record.url?scp=33846015514&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846015514&partnerID=8YFLogxK

U2 - 10.1074/jbc.M608485200

DO - 10.1074/jbc.M608485200

M3 - Article

C2 - 17056594

AN - SCOPUS:33846015514

VL - 281

SP - 39413

EP - 39423

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 51

ER -