- Patient had a PSEN1 E280A mutation, which predisposes you to a 99.9% risk of developing early-onset Alzheimer's.
- Patient was expected to have Alzheimer's by 50. She is currently 70, with very little signs of cognitive decline. Although she has large amounts of amyloid proteins (hallmark of Alzheimer's) it has not reduced her cognitive capacity.
- Patient had two copies of the APOE3ch gene variant. The study indicates this mutation was primarily responsible for protecting the patient from Alzheimer's.
- Imaging tests showed she did have large amounts of amyloid protein deposits, but the amount of tau tangles, was relatively low.
- Experiments have shown this APOE3ch gene variant reduces ability of APOE to bind to certain sugars called heparin sulphate proteoglycans (HSPG). APOE <-> HSPG binding has been implicated as one mechanism that may contribute to amyloid + tau protein deposits.
Correct. The APOE3ch alteration falls within a region of the APOE3 protein. Specifically, the article talks about APOE3 R136S or 'Christchurch' (APOE3ch) mutation.
A more indepth analysis of the patient's mutation and mechanism(s) of action:
I never realised that the APOE variant bound heparin sulfate (HS). HS is actually a cool molecule (glycan) from the perspective of its ability to encode information in its pattern of sulfation.
The signals can be mixed and the precise binding partners for a single molecule can be programmed in. How this is all regulated, and the extent this happens in nature is still being worked out.
- Patient had a PSEN1 E280A mutation, which predisposes you to a 99.9% risk of developing early-onset Alzheimer's.
- Patient was expected to have Alzheimer's by 50. She is currently 70, with very little signs of cognitive decline. Although she has large amounts of amyloid proteins (hallmark of Alzheimer's) it has not reduced her cognitive capacity.
- Patient had two copies of the APOE3ch gene variant. The study indicates this mutation was primarily responsible for protecting the patient from Alzheimer's.
- Imaging tests showed she did have large amounts of amyloid protein deposits, but the amount of tau tangles, was relatively low.
- Experiments have shown this APOE3ch gene variant reduces ability of APOE to bind to certain sugars called heparin sulphate proteoglycans (HSPG). APOE <-> HSPG binding has been implicated as one mechanism that may contribute to amyloid + tau protein deposits.