Individuals with deterministic genes in whom it is known that Alzheimer’s disease (AD) will develop appear to show differences in beta-amyloid distribution when compared with non-dominantly inherited AD patients, helping to consolidate evidence that PET and MRI can depict brain changes well before the arrival of AD-related symptoms, according to preliminary findings presented July 20 at the 2011 Alzheimer’s Association International Conference in Paris.
In approximately 1 percent of AD patients, familial AD is dominantly inherited and guaranteed to present, typically earlier than in most AD patients. Hoping to gain important insights into the disease’s pre-symptomatic developments, researchers in the U.S., U.K. and Australia launched the Dominantly Inherited Alzheimer’s Network (DIAN) in 2008.
With an intended enrollment of 400 patients, more than 100 enrollees with familial AD have thus far completed the four-day regimen of clinical testing, including psychiatric and clinical assessment, blood plasma and cerebrospinal fluid (CSF) assays for amyloid-beta and tan and MRI and PET scans.
Relatively little radiologic information on familial AD has been published to date. Small volumetric MRI studies have indicated that dominant gene carriers show increased cerebral atrophy prior to AD symptom onset, according to a presentation given by Nick C. Fox, MD, from the Dementia Research Centre of the Institute of Neurology at the University College London in London.
Fox also reviewed previous findings of microstructural and functional differences among familial AD patients, which included reduced fractional anisotropy in the fornix, increased functional MRI ( fMRI) activity in temporal gyri during encoding tasks and reduced magnetization transfer ratios in the temporal lobe. Most of these findings, Fox indicated, appear to intensify in the five years prior to symptomatic onset of AD.
Among the 150 patients currently enrolled in the DIAN study, initial carbon-11-labeled Pittsburgh Compound-B (C-11 PiB) PET results have identified a variety of patterns, highlighting prominent striatal uptake and marked occipital uptake in some families, according to results presented by William E. Klunk, MD, PhD, co-director of the Alzheimer Disease Research Center at the University of Pittsburgh Medical Center in Pennsylvania.
“Imaging with C-11 PiB PET has revealed distinct differences in the regional distribution of fibrillar beta-amyloid in dominantly inherited AD compared to sporadic late onset AD with marked uptake in the striatum especially in presymptomatic carriers. These studies also suggest that the deposition of amyloid commences many years before the development of dementia…”
Randall Bateman, MD, associate director of DIAN and an assistant professor of neurology at Washington University School of Medicine in St. Louis, corroborated these interim PET findings, suggesting that other data acquired from DIAN patients thus far indicate that amyloid deposition begins long before the onset of any symptoms.
“Based on what we see in our population, brain chemistry changes can be detected up to 20 years before the expected age of onset,” said Bateman.
Researchers remain at a loss for determining the reasons behind these differences between familial and sporadic AD as viewed on imaging scans. “We don’t know yet why there are these differences. For now, it is an observation of one of the few consistent differences between autosomal dominant and sporadic Alzheimer’s,” Bateman stated.