Alzheimer's Disease Education and Referral Center

PET scans with PiB show beta-amyloid in brains of cognitively normal older adults

May 12, 2009


Two recent NIA-funded studies used novel imaging techniques to explore the possible connection between the buildup of beta-amyloid protein deposits in the brains in living people and the risk of developing Alzheimer’s disease (AD). Abnormal deposits of amyloid in the brain are hallmarks of Alzheimer’s and, until recently, could only be confirmed at autopsy. But as shown in these two studies, researchers are using techniques involving PET (positron emission tomography) scans and tracers to image amyloid deposits in people who are symptom free.

One study found large numbers of beta-amyloid protein deposits in the brains of cognitively normal older adults, suggesting that the deposits alone may not be enough to disrupt cognitive function. The other study showed that known genetic markers for the disease did indeed correlate with greater deposits of amyloid, suggesting that the PET method might eventually result in better and earlier detection of the disease.

In the first study, reported in the Archives of Neurology, researchers used PET with the tracer element Pittsburgh Compound B (PiB) to image the brains of 43 adults, 65 to 88 years old, who did not have clinical AD or mild cognitive impairment, a condition that often precedes AD. They found that the 9 participants with beta-amyloid deposits in at least one brain area performed as well on cognitive tests as the 29 amyloid-negative participants and the 5 participants with “intermediate” evidence of amyloid deposits.

The finding that an older person with “significant amyloid burden” can be cognitively normal suggests a high level of cognitive reserve or that beta-amyloid deposition alone does not lead to AD, write the authors, led by Dr. William E. Klunk of the University of Pittsburgh School of Medicine. Alternatively, some of these individuals may go on to develop AD—in which case PET may be useful in finding signs of AD before clinical symptoms appear. The findings with PiB mirror those previously found in clinicopathological studies, where a proportion of clinically normal people were found to have significant amyloid deposits in their brains after death.

In the second study, published in the Proceedings of the National Academy of Sciences, researchers, led by Dr. Eric Reiman of the Banner Alzheimer’s Institute in Phoenix, conducted PET scans using PiB in 28 cognitively normal older people and correlated the results with the presence of the apolipoprotein E (APOE) ε4 allele, a known risk factor for AD.

The researchers found progressively higher levels of beta-amyloid deposits in carriers with one and two copies of the APOE ε4 than in the noncarriers. They concluded that their findings “support the possibility of using fibrillar beta-amyloid imaging, along with other biomarkers of beta-amyloid, tau, and neuronal pathology and other risk factors, in the preclinical detection and tracking of AD and the evaluation of promising prevention therapies.” Previous autopsy studies have shown that ApoE ε4 carriers have higher levels of amyloid pathology in their brains at  death.

References:

Aizenstein, H.J., et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol. 2008 Nov. 65(11):1509–17.

Reiman, E.M, et al. Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease. Proc Natl Acad Sci USA. 2009 Apr 21. 106(16):6820-25.

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