In the grey matter of the brain, florbetapir binding with amyloid-beta was evident in all the mutation carriers who were aged 30 years or older, regardless of whether they were symptomatic. In contrast, there was no such binding in the noncarriers or in the carriers who were younger than 30 years.
The cerebral pattern of this deposition was similar to that seen in patients with other forms of AD, primarily affecting the posterior cingulate, precuneus, parietotemporal, frontal, and basal ganglial regions, the researchers said (Lancet Neurol. 2012 Nov. 6 [doi:10.1016/S1474-4422(12)70227-2]).
Based on their findings, Dr. Fleisher and his associates estimated that fibrillar amyloid-beta begins to accumulate in the brain about 16 years before the typical onset of mild cognitive impairment and about 21 years before the typical onset of full dementia in familial AD. It seems to peak during the following decade, then plateau just a few years before symptoms start to appear.
It is important to note that the findings of Dr. Fleisher and his colleagues concerning people with autosomal-dominant AD may not be generalizable to more common forms of the disease, Dr. William Jagust wrote in an editorial accompanying the study.
Autosomal-dominant disease is thought to be related to the overproduction of amyloid-beta. In contrast, AD related to the apolipoprotein E genotype "is more closely associated with reduced clearance of amyloid-beta." It is still unclear whether these different mechanisms will respond the same way to amyloid-lowering therapies, said Dr. Jagust of the Helen Wills Neuroscience Institute and the School of Public Health at the University of California, Berkeley (Lancet Neurol. 2012 Nov. 6 [doi:10.1016/S1474-4422(12)70255-7]).
Both studies were funded in part by the Banner Alzheimer’s Foundation, Colciencias, the National Institute on Aging, and the state of Arizona. The florbetapir-PET scan study was funded in part by Avid Pharmaceuticals. The biomarker assay and MRI study also was funded in part by Boston University and the National Institute of Neurological Disorders and Stroke.
Dr. Fleisher reported ties to Eli Lilly and Avid Pharmaceuticals, and his associates reported ties to numerous industry sources. Dr. Jagust reported having served as a consultant to Synarc, TauRx, Genentech, and Siemens. Dr. Fox reported receiving institutional research support from Alzheimer’s Research UK, the Alzheimer’s Society, Bristol-Myers Squibb, Eisai, Elan, GE Healthcare, Janssen, Lilly, Lundbeck, the National Institute for Health Research, the U.K. Medical Research Council, Pfizer/Wyeth, and the Wolfson Foundation.