Amyloid Beta and Immunotherapy

Question 1

What are the 3 post-mortem hallmarks of Alzheimer’s disease?

Answer 1

• Amyloid-containing plaques - outside of cells. (Aβ peptide).
• Formation of neurofibrillary tangles - inside of cell. (Phosphorylated tau).
• ‘Adipose inclusions’ or ‘lipoid granules’ (lipid changes).
• The problem with this is that you can only see this post-mortem.

Question 2

How does amyloid kill cells?

Answer 2

• By attaching to cell surface target receptors.
• By attaching to targets inside the nerve cell.
  
  • This activated signals: death of nerve cells.
• Why is this important?
  
  • Toxic amyloid is first made inside the cell
    
    • This happens well before the amyloid plaques are made (the plaques on the outside are a redherring). This is usually thought to be the cause but it must be made on the inside first.

Question 3

Describe what amyloid does inside the cell.

Answer 3

• There is a target that attaches amyloid inside the cell, called ABAD (amyloid binding alcohol dehydrogenase).
• ABAD normally makes energy for the brain.
• ABAD is in mitochondria.
• Amyloid attaching to ABAd leads to cell death.

Question 4

What does the brain stop using in age?

Answer 4

Glucose. The brain stops using glucose for energy in older age. Many treatments are aimed at working out how to make the brain use glucose again.

Question 5

Why are memories lost in dementia?

Answer 5

• Loss of synaptic connections.
• There are different types of synaptic connections:
  
  • Short term
  • Long term
  • The difference is that in long term memories the synapses are physically bigger.

Question 6

Curing dementia needs to target neurodegeneration. What are the more specific factors to target to prevent neurodegeneration?

Answer 6