Genetically altering aβ distribution from the brain to the vasculature ameliorates tau pathology

Salvatore - Oddo, Antonella Caccamo, David Cheng, Frank M. Laferla

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The inheritance of the ε4 allele of the apolipoprotein E (apoE) gene is the major genetic risk factor for developing late-onset Alzheimer disease. In transgenic mice overexpressing amyloid precursor protein (APP), replacing the endogenous mouse apoE gene with the human apolipoprotein E4 (apoE4) gene alters the distribution of amyloid-β (Aβ) deposits from the brain parenchyma to the vasculature. However, the effects of this distribution on the onset and progression of tau pathology remain to be established. To address this issue, we used a genetic approach to replace the endogenous apoE gene with the human apoE4 allele in the 3xTg-AD mice. We showed that changing Aβ distribution from the parenchyma to the vasculature drastically reduces the tau pathology. The 3xTg-AD mice expressing the human apoE4 gene were virtually depleted of any somatodendritic tau deposits. These data strongly suggest that the somatodendritic tau accumulation is dependent on the parenchyma Aβ deposits.

Original languageEnglish (US)
Pages (from-to)421-430
Number of pages10
JournalBrain Pathology
Volume19
Issue number3
DOIs
StatePublished - Jul 2009
Externally publishedYes

Fingerprint

Apolipoprotein E4
Pathology
Brain
Genes
Apolipoproteins E
Alleles
Amyloid beta-Protein Precursor
Amyloid Plaques
Transgenic Mice
Alzheimer Disease

Keywords

  • Alzheimer
  • ApoE
  • Tangles
  • Tau

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Medicine(all)

Cite this

Genetically altering aβ distribution from the brain to the vasculature ameliorates tau pathology. / Oddo, Salvatore -; Caccamo, Antonella; Cheng, David; Laferla, Frank M.

In: Brain Pathology, Vol. 19, No. 3, 07.2009, p. 421-430.

Research output: Contribution to journalArticle

Oddo, Salvatore - ; Caccamo, Antonella ; Cheng, David ; Laferla, Frank M. / Genetically altering aβ distribution from the brain to the vasculature ameliorates tau pathology. In: Brain Pathology. 2009 ; Vol. 19, No. 3. pp. 421-430.
@article{e1594cfb59414b45b191eeebf8216ce7,
title = "Genetically altering aβ distribution from the brain to the vasculature ameliorates tau pathology",
abstract = "The inheritance of the ε4 allele of the apolipoprotein E (apoE) gene is the major genetic risk factor for developing late-onset Alzheimer disease. In transgenic mice overexpressing amyloid precursor protein (APP), replacing the endogenous mouse apoE gene with the human apolipoprotein E4 (apoE4) gene alters the distribution of amyloid-β (Aβ) deposits from the brain parenchyma to the vasculature. However, the effects of this distribution on the onset and progression of tau pathology remain to be established. To address this issue, we used a genetic approach to replace the endogenous apoE gene with the human apoE4 allele in the 3xTg-AD mice. We showed that changing Aβ distribution from the parenchyma to the vasculature drastically reduces the tau pathology. The 3xTg-AD mice expressing the human apoE4 gene were virtually depleted of any somatodendritic tau deposits. These data strongly suggest that the somatodendritic tau accumulation is dependent on the parenchyma Aβ deposits.",
keywords = "Alzheimer, ApoE, Tangles, Tau",
author = "Oddo, {Salvatore -} and Antonella Caccamo and David Cheng and Laferla, {Frank M.}",
year = "2009",
month = "7",
doi = "10.1111/j.1750-3639.2008.00194.x",
language = "English (US)",
volume = "19",
pages = "421--430",
journal = "Brain Pathology",
issn = "1015-6305",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Genetically altering aβ distribution from the brain to the vasculature ameliorates tau pathology

AU - Oddo, Salvatore -

AU - Caccamo, Antonella

AU - Cheng, David

AU - Laferla, Frank M.

PY - 2009/7

Y1 - 2009/7

N2 - The inheritance of the ε4 allele of the apolipoprotein E (apoE) gene is the major genetic risk factor for developing late-onset Alzheimer disease. In transgenic mice overexpressing amyloid precursor protein (APP), replacing the endogenous mouse apoE gene with the human apolipoprotein E4 (apoE4) gene alters the distribution of amyloid-β (Aβ) deposits from the brain parenchyma to the vasculature. However, the effects of this distribution on the onset and progression of tau pathology remain to be established. To address this issue, we used a genetic approach to replace the endogenous apoE gene with the human apoE4 allele in the 3xTg-AD mice. We showed that changing Aβ distribution from the parenchyma to the vasculature drastically reduces the tau pathology. The 3xTg-AD mice expressing the human apoE4 gene were virtually depleted of any somatodendritic tau deposits. These data strongly suggest that the somatodendritic tau accumulation is dependent on the parenchyma Aβ deposits.

AB - The inheritance of the ε4 allele of the apolipoprotein E (apoE) gene is the major genetic risk factor for developing late-onset Alzheimer disease. In transgenic mice overexpressing amyloid precursor protein (APP), replacing the endogenous mouse apoE gene with the human apolipoprotein E4 (apoE4) gene alters the distribution of amyloid-β (Aβ) deposits from the brain parenchyma to the vasculature. However, the effects of this distribution on the onset and progression of tau pathology remain to be established. To address this issue, we used a genetic approach to replace the endogenous apoE gene with the human apoE4 allele in the 3xTg-AD mice. We showed that changing Aβ distribution from the parenchyma to the vasculature drastically reduces the tau pathology. The 3xTg-AD mice expressing the human apoE4 gene were virtually depleted of any somatodendritic tau deposits. These data strongly suggest that the somatodendritic tau accumulation is dependent on the parenchyma Aβ deposits.

KW - Alzheimer

KW - ApoE

KW - Tangles

KW - Tau

UR - http://www.scopus.com/inward/record.url?scp=65649106997&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65649106997&partnerID=8YFLogxK

U2 - 10.1111/j.1750-3639.2008.00194.x

DO - 10.1111/j.1750-3639.2008.00194.x

M3 - Article

C2 - 18657136

AN - SCOPUS:65649106997

VL - 19

SP - 421

EP - 430

JO - Brain Pathology

JF - Brain Pathology

SN - 1015-6305

IS - 3

ER -