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Alzheimer’s Disease (AD) Model

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Alzheimer’s disease (AD) is the most common neurodegenerative disorder and the leading cause of dementia. Clinically, AD is characterized by a decline in cognitive abilitiesbeginning with mild cognitive impairment and eventually progressing to severe intellectual disability and an inability to manage daily life.


Neuropathologically, AD is defined by the presence of fibrillar amyloid β (Aβ) peptide in extracellular senile plaques and Tau filaments in intracellular neurofibrillary tangles (NFT).

Model Construction and Testing Services

1. AD Transgenic Models

Transgenic models involve genetic modification of existing genes or alteration of the location of target genes on normal chromosomes. To understand the pathogenesis of AD, various transgenic mouse models have been developed to accelerate the accumulation of Aβ and Tau tangles. These include different strains such as APP23, TgCRND8, APPPS1, etc.


● Case

Using pronuclear microinjection, two separate transgenic constructs encoding human APPSwe and TtauP301L (4R/0N) were co-injected into single-cell embryos from homozygous PS1M146V knock-in mice. Embryos carrying the APP and Tau genes were transferred into recipient mice, and subsequent offspring were genotyped to identify 3×Tg-AD mice. Western blot analysis revealed elevated levels of APP and Tau proteins in the brains of these transgenic mice.


 

Figure 1. Construction and Identification of the 3×Tg-AD Mouse Model

 

Reference:

Oddo S, Caccamo A, Shepherd JD, et al. Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron. 2003 Jul 31;39(3):409-21.



2. AAV-Induced AD Model (Developed by Genevoyager)

We develop AD models by expressing AAV-mediated genes via different administration routes.


● Case 1

An AAV-AD model was generated by expressing Tau or APP protein in the hippocampal region of mice via stereotactic injection of AAV. After 12 weeks, analysis of the mouse brain revealed significant expression of APP.SLA in pyramidal neurons of the CA region and cortex. Antibody 6E10 showed extensive accumulation of APP metabolites within the neurons. Western blot analysis demonstrated that the relative levels of APP.SLA or TauP301L in hippocampal extracts were approximately twice as high as endogenous mouse APP or TauP301L, respectively. Six months after intracerebral injection of AAV-APP.SLA, amyloid plaques appeared, along with phosphorylated Tau in dystrophic axons surrounding the plaques.