Cytoskeleton-related Alzheimer's Disease Research Service

Mechanisms of Alzheimer's Disease

Alzheimer's disease (AD) is the leading cause of dementia and is a progressive neurodegenerative disease. Dementia includes memory loss and difficulties with thinking, language, and problem-solving skills.

• Aβ Plaque Associated Neurodegeneration: Aβ plaques form and are deposited in different areas of the brain. These plaques are recognized by the brain as foreign bodies and trigger inflammatory and immune responses by activating microglia and releasing cytokines, ultimately leading to cell death and neurodegeneration.
• Neurofibrillary Degeneration: Over-activation of cyclin-dependent kinase 5 (CDK5) and leads to tau hyperphosphorylation. Hyperphosphorylation leads to a decrease in the affinity of tau proteins for microtubules. The hyperphosphorylated tau forms NFTs and is deposited in the cytoplasm where it no longer functions to maintain cellular structure.
• Neuroinflammation: Neuro-inflammation plays a central role in the pathogenesis of AD. Acute inflammation has a protective role in defending against brain injury such as the presence of Aβ plaque.

The Abnormal tau Modification Theory of Alzheimer's Disease

TAU protein is a microtubule-associated protein. Under normal conditions phosphorylated tau protein binds to microtubules, helps maintain their dynamic stability, and plays an important role in neuronal material transport and information transmission.

The abnormal modification of tau protein in Alzheimer's disease is believed to be the result of hyperphosphorylation, which weakens the ability of tau protein to bind to microtubule proteins, destroying the cytoskeleton and producing abnormal neurofibrillary tangles (NFTs) that can be observed under light microscopy, while the microtubules are unable to transport relevant substances due to deformation, and the axons and dendrites of distal neurons atrophy due to lack of nutrients, thus triggering Alzheimer's disease. 

Tau and Aβ PET images in cognitively healthy controls (top-CDR0) and AD patients (bottom-CDR>0) [1].

Services

• Alzheimer's Disease Model Construction
  We offer cytoskeleton-associated gene knockout, knock-in or conditional knockout mouse models or custom disease models to help you make breakthroughs in your Alzheimer's research.
  • Tau Mutant Mouse Model
  • Nestin Mutant Mouse Model

• Alzheimer's Disease Cytoskeletal Antibody Development
  We offer a range of tau protein antibodies with different phosphorylation sites, as well as antibodies to other Alzheimer's disease cytoskeletal proteins, to assist our clients in their Alzheimer's research.

• Cytoskeletal Compounds Screening for Alzheimer's Disease
  We have a well-established antibody development process and an extensive compound library to help our customers conduct disease-related research by providing compound screening services for Alzheimer's-related proteins, including Aβ and Tau.