This, researchers at the Florey Institute of Neuroscience and Mental Health say will help fine-tune their approach when designing anti-Alzheimer’s disease drugs that remove the protein.
Dr Blaine Roberts and his team in Melbourne found the average difference in the amount of the beta amyloid protein that separates normal conditions from Alzheimer’s disease is a just 5 mg.
At the same time, they determined that beta amyloid sitting inside the cell membrane is likely to be the disease-causing agent in Alzheimer’s, not the soluble form of beta amyloid which is released from the surface of a neuron.
Published in the journal Brain the, Dr Roberts’ work also isolated the four distinct cellular locations of beta amyloid in both healthy brains and those from Alzheimer’s patients. Dr Roberts concludes that the pool of soluble amyloid, commonly thought to cause the disease, only comprises less than half a percent of the total amyloid in the brain.
The finding is especially important because it confirms that it is extremely unlikely for this soluble form of amyloid to be the only source of neurotoxicity in the Alzheimer's disease process.
“It is in fact the amyloid that is locked up in a brain cell’s membrane, half of the total amount that is likely to be doing the damage in Alzheimer’s,” Dr Roberts says.
As part of their research, post-mortem brain analyses scans were compared to living participant scans, allowing the team to calculate the speed at which the protein accumulates. Findings showed it takes more than 19 years for the protein to build up to a dangerous level.
Dr Roberts’ precise quantitation will enable clinicians to determine exactly how much amyloid a patient has in their brain, and therefore precisely tailor the dose of experimental new medications.
These could include amyloid antibodies or enzyme inhibitors to clear just enough amyloid to extend healthy life by five years, for example, without inducing some of the anticipated, possibly severe, side effects.