Humanized Apolipoprotein E (ApoE) based Neurodegeneration Models
ApoE is a plasma protein involved in cholesterol transport, with three human isoforms (E2, E3, and E4). ApoE is a major risk factor for cardiovascular disease.
The ApoE gene is also the strongest genetic risk factor for sporadic forms of late-onset Alzheimer Disease (AD).
In the brain, apoE is primarily synthesized by astrocytes and microglia, and is lipidated by the ABCA1 transporter to form lipoprotein particles. Lipidated apoE binds to soluble Aβ and facilitates Aβ uptake through cell surface receptors.
The association of specific apoE isoform expression with human neurodegenerative disorders has focused attention on the role of these apoE isoforms in lipoprotein receptor-dependent synaptic modulation.
Among the three isoforms, apoE4 appears to drive amyloid pathology by inhibiting brain clearance of amyloid-β (Aβ) peptides and by promoting Aβ aggregation.
Targeting apoE and apoE receptor pathways represents promising therapeutic strategies to combat neurodegenerative diseases such as Alzheimer’s.
Taconic provides three humanized apoE mouse models that are useful for studying the role of human APOE polymorphism neurodegenerative disorders.