PET tracer gauges effectiveness of promising Alzheimer's treatment

December 6, 2017, Society of Nuclear Medicine and Molecular Imaging
PET imaging shows the average 18F-AV45 uptake per animal group at 8 and 13 months of age. A significant interaction of genotype treatment was observed in the cortex (p = 0.0248), hippocampus (p = 0.0071) and thalamus (p = 0.0084), indicating reduced [18F]-AV45 uptake in BACE1 inhibited transgenic mice. Credit: MICA, University of Antwerp, Belgium

In the December featured basic science article in The Journal of Nuclear Medicine, Belgian researchers report on the first large-scale longitudinal imaging study to evaluate BACE1 inhibition with micro-PET in mouse models of Alzheimer's disease. PET imaging has been established as an excellent identifier of the amyloid plaque and tau tangles that characterize Alzheimer's disease. Now it is proving to be an effective way to gauge treatment effectiveness.

The tracer makes it possible to image the effects of chronic administration of an inhibitor for an enzyme, called beta (β)-site amyloid precursor protein-cleaving enzyme 1 (BACE1), which cuts off protein fragments that can lead to amyloid-β development and is more prevalent in brains affected by Alzheimer's. It does this by binding to BACE1.

The study compared with those genetically-altered to have Alzheimer's, and tested 18F-florbetapir (18F-AV45) along with two other tracers, 18F-FDG PET and 18F-PBR111. The mice received the BACE inhibitor at 7 weeks, then brain metabolism, neuroinflammation and amyloid-β pathology were measured using a micro-PET (μPET) scanner and each of the tracers. Baseline scans were done at 6-7 weeks and follow-up scans at 4,7 and 12 months. 18F-AV45 uptake was measured at 8 and 13 months of age. After the final scans, microscopic studies were performed.

While all three tracers detected pathological differences between the genetically modified mice and the controls, only 18F-AV45 showed the effects of inhibitor treatment by identifying reduced amyloid-β pathology in the genetically modified mice. This was confirmed in the microscopic studies.

The team of the Molecular Imaging Center Antwerp, Belgium, however warns, "This study clearly showed that accurate quantification of amyloid-beta tracers is critically important and that the non-specific uptake in the brain of subjects might be underestimated for some existing Alzheimer's tracers that have fast metabolization profiles. The aim of this translational research is advancing results discovered at the bench so that they can be applied to patients at the bedside."

The statistics on Alzheimer's are sobering. Approximately 10 percent of people 65 and older have Alzheimer's dementia, according to the Alzheimer's Association. More than 5 million Americans are living with the disease, and that number could rise to 16 million by 2050.

Explore further: Alzheimer's disease might be a 'whole body' problem

More information: Steven Deleye et al, Evaluation of Small-Animal PET Outcome Measures to Detect Disease Modification Induced by BACE Inhibition in a Transgenic Mouse Model of Alzheimer Disease, Journal of Nuclear Medicine (2017). DOI: 10.2967/jnumed.116.187625

Related Stories

Alzheimer's disease might be a 'whole body' problem

October 31, 2017
Alzheimer's disease, the leading cause of dementia, has long been assumed to originate in the brain. But research from the University of British Columbia and Chinese scientists indicates that it could be triggered by breakdowns ...

Steering an enzyme's 'scissors' shows potential for stopping Alzheimer's disease

July 19, 2017
The old real estate adage about "location, location, location" might also apply to the biochemical genesis of Alzheimer's disease, according to new research from the University of British Columbia.

BACE-Inhibitor successfully tested in Alzheimer's animal model

July 28, 2017
The protein amyloid beta is believed to be the major cause of Alzheimer's disease. Substances that reduce the production of amyloid beta, such as BACE inhibitors, are therefore promising candidates for new drug treatments. ...

Single dual time-point PET scan identifies dual Alzheimer's biomarkers

June 14, 2017
More people die of Alzheimer's disease than prostate and breast cancer combined. Identifying the disease before major symptoms arise is critical to preserving brain function and helping patients maintain quality of life. ...

Team finds regulator of amyloid plaque buildup in Alzheimer's disease

January 23, 2014
Scientists from the Florida campus of The Scripps Research Institute have identified a critical regulator of a molecule deeply involved in the progression of Alzheimer's disease.

Brain enzyme is double whammy for Alzheimer's disease

August 20, 2012
The underlying causes of Alzheimer's disease are not fully understood, but a good deal of evidence points to the accumulation of β-amyloid, a protein that's toxic to nerve cells. β-amyloid is formed by the activity ...

Recommended for you

Scientists discover why some people with brain markers of Alzheimer's have no dementia

August 16, 2018
A new study from The University of Texas Medical Branch at Galveston has uncovered why some people that have brain markers of Alzheimer's never develop the classic dementia that others do. The study is now available in the ...

Researchers identify new genes that may contribute to Alzheimer's disease

August 14, 2018
Researchers from Boston University School of Medicine, working with scientists across the nation on the Alzheimer's Disease Sequencing Project (ADSP), have discovered new genes that will further current understanding of the ...

Deaths from resident-to-resident incidents in dementia offers insights to inform policy

August 14, 2018
Analyzing the incidents between residents in dementia in long-term care homes may hold the key to reducing future fatalities among this vulnerable population, according to new research from the University of Minnesota School ...

Scientists propose a new lead for Alzheimer's research

August 14, 2018
A University of Adelaide-led team of scientists has suggested a potential link between iron in our cells and the rare gene mutations that cause Alzheimer's disease, which could provide new avenues for future research.

Eye conditions provide new lens screening for Alzheimer's disease

August 8, 2018
Alzheimer's disease is difficult to diagnose as well as treat, but researchers now have a promising new screening tool using the window to the brain: the eye.

Potential indicator for the early detection of dementias

August 7, 2018
Researchers at the University of Basel have discovered a factor that could support the early detection of neurodegenerative diseases such as Alzheimer's or Parkinson's. This cytokine is induced by cellular stress reactions ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.