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The Progression of Beta-Amyloid Deposition in Alzheimer’s Disease as Assessed by PET Imaging

  • Author(s): Malatt, Camille
  • et al.
Abstract

Alzheimer’s Disease has increasingly become a national health concern with the growth of the aging population. While there are currently no effective disease-modifying treatments, there is a need for biomarkers that could be used in early diagnosis of the disease and in measuring efficacy of therapeutics in clinical trials. Beta-amyloid peptide in particular is thought to play a critical role in the pathogenesis of the disease. Especially with the advent of Florbetapir, a new compound that will facilitate more accessible and accurate amyloid-PET imaging, beta-amyloid could become an even more valuable biomarker. While useful in early detection of AD, it is not clear if it has utility in staging AD’s progression. The biomarker cascade model states that beta-amyloid levels plateau before the onset of clinical symptoms, and thus do not have a direct relationship with cognitive decline, suggesting that amyloid-PET imaging provides little information about disease stage. However, most data supporting this hypothesis have been based on quantification of amyloid load using standardized uptake value ratios (SUVr), which is limited in neurodegenerative disease where progressive regional atrophy can be confounded with levels of regional amyloid deposition. For example, SUVr relies on warping all patients’ brain images to a standardized “template” space, yet success in matching a brain to template space is inversely related to the degree of brain atrophy. Also, SUVr is typically measured across a subset of select cortical regions that are known to show elevated amyloid in early disease. We challenge this model by studying the change in both global and regional deposition of beta-amyloid in healthy controls, mild cognitive impairment (MCI) patients, and AD patients using quantification of amyloid binding in each subject’s “native-space,” along with atrophy correction. We hope to show that beta-amyloid levels do not completely saturate, but instead continue to increase during the progression of the disease. This would suggest that amyloid-PET imaging contains some information about the stage or severity of disease in both MCI and AD patients, and thus would have some value in aiding in predictive prognosis.

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