Role In Alzheimer's Disease

 Basic Facts: Alzheimer's Disease

• Alzheimer's is a degenerative disease, the most common form of dementia. 
• Most commonly diagnosed in people over the age of 65. 
• Early stage symptoms include inability to acquire new memories, diagnosis is usually via cognitive and behavioural tests.
• As the disease develops, sympotoms such as irritability, aggression, long term memory loss and speech difficulties.
• The disease is associated with neurofibrillary tangles and amyloid plaques in the brain.

The Role of Delta-Notch Pathway in development of Alzheimer's Disease:

ɣ-Secretase (Presenilin) used to cleave within the Notch pathway is also used in the brain to cleave APP (amyloid precursor protein). APP has two potential cleavage sites for ɣ-secretase. Depending on which site the cleavage is made at, two different lengths of extracellular peptides can be produced; one is 40 amino acids long, the other 42 amino acids long. It is the 42 amino acid protein which is a major constituent of amyloid plaques associated with Alzheimer's disease. 

(Image Portays the two possible cleavages of APP by ɣ-Secretase, leading to two different lengths of peptide. Image Courtesey of: Wikimedia)

What happens after cleavage? 

In a healthy brain the 40 long peptides are easily broken down, where as in an Alzhimer's patient the 42 long peptide fragments accumulate to form hard, insoluble plaques. It is these plaques and insoluble neurofibrillary tangles that are major causes of neuron degredation and subsequently Alzheimer's disease.