New Imaging Compounds for Alzheimer's Protein Deposits in the Brain Show that Different Forms of the APOE Risk Gene Create Diffe
Posted Jul 15 2010 10:07am
Alzheimer's Reading Room
"The findings support our hypothesis that APOE genotype changes amyloid structure,"...."This is important because the different shapes might respond differently to treatments that attempt to clear amyloid deposits from the brain." -- Sam Gandy, Mount Sinai School of Medicine
A new class of biomarkers has been discovered that can stick to protein structures in the body and emit colors reflecting the different shapes or forms of the proteins. They are called luminescent conjugated oligothiophenes (LCOs) or luminescent conjugated polymers (LCPs). Among other uses, they are currently being employed in test tubes, animal models and autopsied Alzheimer's brains to study the structure of proteins deposits caused by the disease. The new markers bind to the two well-established hallmarks of Alzheimer's – beta amyloid plaques and tau tangles – and glow different colors depending on which forms of the deposits they "stick" to (e.g., plaques often "glow" orange, while tangles "glow" yellowish green).
In this study reported at AAICAD 2010, Sam Gandy, MD, PhD, of Mount Sinai School of Medicine, New York, and colleagues used LCOs/LCPs to investigate the possibility that the shape of brain protein deposits in people with Alzheimer's who have the APOE ε4/ε4 gene type (highest risk) is different from those having APOE ε3/ε3 (neutral risk).
Frozen brain sections from people who died with Alzheimer's were stained using two LCPs/LCOs: pentamer formyl thiophene acetic acid (pFTAA) and polythiophene acetic acid (PTAA). Using PTAA, the researchers observed that Alzheimer patients with APOE ε4/ε4 had core and cerebrovascular amyloid of different shapes, while in people with APOE ε3/ε3 the two amyloid structures had the same shape. Using pFTAA revealed that tau tangle densities in ε4/ε4 Alzheimer patients that were apparently greater than those with ε3/ε3.
"The findings support our hypothesis that APOE genotype changes amyloid structure," Gandy said. "This is important because the different shapes might respond differently to treatments that attempt to clear amyloid deposits from the brain."
In some recent drug trials, the experimental therapy provided benefits in people who had a certain type of the APOE gene (known as ε3) but were less or not effective in another type (ε4).
LCOs/LCPs were pioneered by Peter Nilsson of the Department of Chemistry, Linköping University, Sweden. The study also involved collaborating teams from Charité – Universitätsmedizin Berlin, Germany (led by Frank Heppner), Washington University, St Louis (led by David Holtzman), and other labs at Mount Sinai (led by Patrick Hof and Dara Dickstein).
--Hannah Brautigam, Sam Gandy, et al. New Conformation-Sensing Imaging Compounds Distinguish Protein Deposits In APOE e3/e3 Alzheimer's Patients From That In APOE e4/e4 Alzheimer's Patients. (Funded by: National Institutes of Health, Cure Alzheimer's Fund, European Union FP7 HEALTH (Project LUPAS), German Research Foundation, Knut and Alice Wallenberg Foundation, Swedish Foundation for Strategic Research)
The Alzheimer's Association International Conference on Alzheimer's Disease (AAICAD) is the world's largest conference of it's kind, bringing together researchers from around the world to report and discuss groundbreaking research and information on the cause, diagnosis, treatment and prevention of Alzheimer's disease and related disorders. As a part of the Alzheimer's Association's research program, AAICAD serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.
Bob DeMarco is the editor of the Alzheimer's Reading Room and an Alzheimer's caregiver. Bob has written more than 1,640 articles with more than 11,000 links on the Internet. Bob resides in Delray Beach, FL.