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Neuroscience. 2015 Jan 22;284:99-106. doi: 10.1016/j.neuroscience.2014.09.045. Epub 2014 Sep 28.

A novel rat model of Alzheimer's disease based on lentiviral-mediated expression of mutant APP.

Author information

1
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2
Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3
Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA.
4
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
5
NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: l.dargahi@sbmu.ac.ir.

Abstract

BACKGROUND:

Alzheimer's disease (AD) is characterized by progressive and irreversible cognitive and memory impairment. The discovery of familial forms of AD (fAD) in association with specific gene mutations facilitated the generation of numerous rodent models. These models in turn proved valuable for the study of molecular mechanisms underlying AD pathogenesis, and facilitated translational research and preclinical drug development. This study aimed to introduce a new rat model of AD simulating some aspects of the sporadic cases of disease.

METHODS:

Lentiviruses (LV) encoding human amyloid protein precursor (APP) bearing the fAD-linked Swedish and Indiana mutations (APPSw/Ind) were injected bilaterally in the hippocampus of adult rats. Passive avoidance and spatial memory performance were assessed 30 and 45 days post-injection, respectively. APP overexpression, intracellular accumulation of β-amyloid (Aβ) peptide, and astrogliosis were also evaluated using immunohistochemical procedures.

RESULTS:

Passive avoidance memory deficit was followed by impairments in spatial memory retrieval in LV (APPSw/Ind)-injected rats, compared to control animals. In addition, LV expression of APPSw/Ind was associated with intraneuronal accumulation of Aβ, and reactive astrocytosis, two major AD hallmarks.

CONCLUSION:

Results from this work suggest that LV-mediated delivery of APPSw/Ind in adult rats represents a cost and time-effective animal model for the study of mechanisms underlying APP-linked fAD pathogenesis. The relevance of this animal model to the study of sporadic AD is discussed.

KEYWORDS:

Alzheimer’s disease; animal model; lentiviral vector

[Indexed for MEDLINE]

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