The differential diagnosis study, lead by Dr. Victor Villemagne of the Austin Hospital, Melbourne, used florbetaben PET imaging in 26 Alzheimer's patients, 11 with frontotemporal lobar degeneration (FTLD), 6 with Lewy body dementia (LBD), and 26 healthy controls.
The Alzheimer's patients showed significantly higher uptake of the compound in neocortical areas compared with all the other groups.
Nearly all of the Alzheimer's patients (96%) showed diffuse cortical uptake, whereas only white matter binding was seen in most of the healthy controls (85%), FTLD patients (91%), and LBD patients (67%).
“This should not be surprising, because frontotemporal dementia is a tauopathy, not related to amyloid, and Lewy body patients and normal controls should not have amyloid in their brain,” Dr. Sabbagh said. “It's reasonable to say that this compound has the potential to discriminate one form of cognitive disorder from another.”
Both florbetaben studies were sponsored by Bayer Schering Pharma. Dr. Villemagne and Dr. Sabri have both received research grants and support from the company.
Plaque Differences Detected
New agents called luminescent conjugated oligothiophenes (LCOs) are beginning to reveal to scientists how APOE status affects the way in which beta-amyloid protein aggregates in the brain of Alzheimer's patients.
These compounds have shown that Alzheimer's patients with a double copy of APOE e4 develop beta-amyloid aggregates in brain blood vessels that are clearly different in structure or conformation from the aggregates in the brain substance, while in those who are homozygous for the APOE e3 allele, the protein clumps in both the vascular and core structures take on apparently identical conformation, said Dr. Samuel E. Gandy, who serves as associate director of the Alzheimer's Disease Research Center at Mount Sinai School of Medicine, New York.
LCOs intercalate into protein structures and fluoresce different colors depending on the discrete conformational shape they take when encountering different proteins.
When the compounds encounter amyloid plaques, they tend to glow orange; when they encounter neurofibrillary tau tangles, they tend to glow yellowish green.
Dr. Gandy has been an adviser or consultant for Amicus Therapeutics Ltd.; DiaGenic ASA; Elan Pharmaceuticals Inc.; and Johnson & Johnson Pharmaceutical Research & Development, LLC.
Oligothiophenes glow yellow in amyloid from patients with APOE e4/e4, and orange in those with APOE e3/e3.
Source Images Courtesy Dr. Samuel E. Gandy
A florbetapir PET scan shows more amyloid (red) in an Alzheimer's patient (bottom) than in a healthy volunteer.
Source Courtesy Avid Radiopharmaceuticals Inc.