Researchers have shown that clearance of the substance amyloid-beta that forms plaques is impaired in individuals with Alzheimer’s. A group of 12 individuals with early Alzheimer’s were compared to 12 cognitively normal individuals of the same age. Amyloid-beta was produced at the same average rate by both groups, but in the Alzheimer’s group there was an average drop in the clearance rates of about 30%.
Amyloid-beta was long ago recognized as an important component of the plaques in the brain found during the autopsies of individuals who had Alzheimer’s. One way the brain eliminates the amyloid-beta typically produced by cell activity in the brain is by moving it to the spinal fluid for disposing of. A drop in levels of amyloid-beta in spinal fluid could be a presymptomatic Alzheimer’s indicator, possibly because amyloid-beta is sticking in the brain and beginning to accumulate there.
Failures of therapies meant to clear the brain’s amyloid-beta have resulted in some researchers speculating that amyloid-beta might not be causatively associated with Alzheimer’s. The current study however shows that Alzheimer’s is linked to disruption of the ability of the brain to handle amyloid-beta normally.
SILK (stable isotope-linked kinetics) was used to assess amyloid-beta clearance and production rates.
During SILK, individuals were given a labeled amino acid leucine via an intravenous drip.
Brain cells pick up the labeled leucine over the course of hours and it’s incorporated into new copies of amyloid-beta and other proteins they make. Periodic samples of the individuals’ cerebrospinal fluid were taken through a lumbar catheter, the amyloid-beta from the samples was purified and the amount of the amyloid-beta which included labeled leucine was determined.
The individuals’ amyloid-beta production rate was determined by tracking the rise of the labeled leucine amyloid-beta over time. When the percentage of labeled leucine amyloid-beta plateaus, the introduction of labeled leucine was stopped. The individuals’ cerebrospinal fluid continued to be periodically sampled, which allowed the rate the nervous system cleared out the labeled amyloid-beta to be measured.
There was a significant difference of the average clearance rate for amyloid-beta between the 12 early Alzheimer’s individuals and the 12 normal individuals.