APOE3 Christchurch: A New Anti-Amyloid Therapy for Alzheimer’s in a Patient Announced by a Frustrated Amyloid Patient
Piedrahita used to joke that she had a “golden brain”, and a scan revealed what she might have meant. Her brain contained extremely high levels of amyloid-β plaques, but minimal neuroinflammation. Something else was missing, too. Kosik, who was at the University of California, Santa Barbara, says that the tangles of the brain inflammation called plaques spared most of the brain. The plaques in her brain were not enough to cause cognitive issues, and we learned something that was important right away.
As well as developing and screening small molecule compounds that could be easier to deliver into the brain,Huang and his group are also looking for genes that could be used to create new therapies. Holtzman is pursuing drugs inspired by the Christchurch mutation, with a focus on cells in the brain known as microglia.
Piedrahita had two copies of the most common version, APOE3. Her variant was called APOE3 Christchurch or APOE3Ch. This mutation affects how the APOE protein binds to a sugar–protein compound called HSPG, which helps tau to propagate through the brain. APOE3Ch showed the lowest affinity for HSPG of any form of the protein; APOE4 showed the highest3.
She was shown to have a different version of the PSEN1 gene. She had a variation of the gene. One form of this gene is a factor in Alzheimer’s disease. There are two other versions that typically have no effect.
There is someone in every family who is against the grain. In this case, it is a person whose story challenges scientists’ understanding of Alzheimer’s disease pathology.
It might be difficult to understand just how tough a diagnosis of Alzheimer’s disease can be for an individual and their family until you have experienced it personally. Unfortunately, too many of us will come to know that there are around seven million new cases of Alzheimer’s every year.
The first disease-modifying therapies for Alzheimer’s target the peptide amyloid-β, which clumps together in the brain. Clearing these deposits slows cognitive decline. To achieve stronger effects, you have to build on Anti-Amyloid Therapy or combine it with other drugs that target other aspects of the disease.
The past five years have seen the development of some blood tests that can distinguish Alzheimer’s from other forms of dementia. It is already apparent that there are serious concerns surrounding the misuse of these diagnostics, including by consumers.
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