Identification and modification of amyloid-independent phenotypes of APOE4 mice

Autor: Joshua Newman, Amanda M. DiBattista, Sonya B. Dumanis, G. William Rebeck
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Apolipoprotein E
Dendritic spine
Apolipoprotein E4
Peroxisome proliferator-activated receptor
Ibuprofen
Pharmacology
Mice
0302 clinical medicine
Neurons
chemistry.chemical_classification
Anti-Inflammatory Agents
Non-Steroidal
Age Factors
Brain
Phenotype
Neurology
Female
lipids (amino acids
peptides
and proteins)
Alzheimer's disease
medicine.drug
Agonist
Amyloid
medicine.medical_specialty
Genotype
medicine.drug_class
Dendritic Spines
Mice
Transgenic
Article
03 medical and health sciences
Developmental Neuroscience
Alzheimer Disease
Internal medicine
mental disorders
medicine
Animals
Humans
Hypoglycemic Agents
Cyclooxygenase 2 Inhibitors
Pioglitazone
business.industry
medicine.disease
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Endocrinology
chemistry
Celecoxib
Thiazolidinediones
business
Protein Processing
Post-Translational
human activities
030217 neurology & neurosurgery
Zdroj: Experimental Neurology. 280:97-105
ISSN: 0014-4886
DOI: 10.1016/j.expneurol.2016.04.014
Popis: Background Over 70 million Americans inherit the strongest genetic risk factor for Alzheimer's disease (AD), apolipoprotein E4 ( APOE4 ), but have no course for reducing their risk. The association of non-steroidal anti-inflammatory drug (NSAID) use with reduced risk of AD for APOE4 -carriers suggests that NSAIDs may be useful in AD prevention. Methods We identified phenotypes associated with APOE4 in APOE knock-in mice in order to define modifiable measures that correlate with risk of AD. Results APOE4 mouse brains showed altered post-translational modifications and biochemical distribution of APOE compared to APOE3 mice; these differences were also observed in brains of human APOE4 carriers. Two-month treatment with ibuprofen significantly altered the expression pattern of APOE in APOE4 mice to that of APOE3 mice; PPAR-γ agonist pioglitazone also had a significant effect. APOE4 mice also show deficits in dendritic spine density, and ibuprofen and pioglitazone significantly increased dendritic spine density. Conclusions We report new phenotypes associated with APOE4 in human and APOE knock-in mice and their mitigation with NSAID treatment, through COX-2 inhibition and PPAR-γ activation.
Databáze: OpenAIRE
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