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Cited by 33Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Genetically Altering Aβ Distribution from the Brain to the Vasculature Ameliorates Tau Pathology

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Oddo, Salvatore, Caccamo, Antonella, Cheng, David, LaFerla, Frank M.·2009·Brain Pathology
DOI 10.1111/j.1750-3639.2008.00194.xPMC PMC4072242
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Abstract

The inheritance of the epsilon4 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-beta (Abeta) 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 Abeta 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 Abeta deposits.

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Cited by

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Authors
Oddo, S., Caccamo, A., Cheng, D., & LaFerla, F. M.
Affiliations
University of California, Irvine (US)
ORCID
Venue
Brain Pathology
Publisher
Wiley
Published
2009-06-10
Volume
19
Issue
3
Pages
421-430
ISSN
  • 1015-6305 (ISSN-L)
  • 1750-3639
DOI
10.1111/j.1750-3639.2008.00194.x
PMC
PMC4072242
OpenAlex
W2028902657
Cited by
33
References
6
Citations by year
2025: 1 · 2024: 1 · 2023: 1 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 4 · 2014: 1 · 2012: 3
FWCI
1.81
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Brain Pathology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (R00AG029729, P01AG000538, AG0212982, AG029729A, K99AG029729, R01AG021982)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
APOE ε4, tau pathology, Alzheimer's disease, 3xTg-AD mice, amyloid precursor protein overexpression
MeSH terms
Alzheimer Disease, Animals, Brain, Enzyme-Linked Immunosorbent Assay, Humans, Immunohistochemistry, Mice, Transgenic, Blotting, Western, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Neurofibrillary Tangles, tau Proteins, Mice, Apolipoprotein E4

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