Impact of amyloid imaging on drug development in Alzheimer's disease

Abstract

Imaging agents capable of assessing amyloid-beta (Aβ) content in vivo in the brains of Alzheimer's disease (AD) subjects likely will be important as diagnostic agents to detect Aβ plaques in the brain, to help test the amyloid cascade hypothesis of AD, and as an aid to assess the efficacy of anti-amyloid therapeutics currently under development and in clinical trials. Positron emission tomography (PET) imaging studies of amyloid deposition in human subjects with several Aβ imaging agents are currently underway. We reported the first PET studies of the carbon-11-labeled thioflavin-T derivative Pittsburgh Compound B ([ 11 C]PiB) in 2004, and this work has subsequently been extended to include a variety of subject groups including AD, mild cognitive impairment (MCI), and healthy controls. The ability to quantify regional Aβ plaque load in the brains of living human subjects has provided a means to begin to apply this technology as a diagnostic agent to detect regional concentrations of Aβ plaques and as a surrogate marker of therapeutic efficacy in anti-amyloid drug trials.

Structural and Functional Imaging Correlates of Cognitive and Brain Reserve Hypotheses in Healthy and Pathological Aging

“…Particularly, since amyloid burden has been suggested as an early, accurate diagnostic tool for AD (Mathis et al 2007;Weiner 2009), the contribution of these studies to the assessment of reserve could partially cope with some of the limitations mentioned in the introduction, providing an objective measure of brain burden. Thus, it is possible now to study patients with the same level of pathology and different cognitive strengths and more interestingly, healthy elders harboring AD pathology, defined as preclinical AD in the new lexicon (Dubois et al 2010).…”

Can we improve care for patients with dementia?

“…positron emissions tomography (pet) scanning with glucose proved a useful early technique that differentiated between alzheimer's fronto-temporal dementia and normal individuals (50). the pittsburgh B agent pet scanning is excellent at detecting amyloid-beta protein (51). It demonstrates increased amyloid deposits in persons with normal memory prior to the development of alzheimer's disease (52).…”

Small molecule inhibitors of Aβ‐aggregation and neurotoxicity

“…Although dye-based therapeutics have so far not reached clinical trials, these compounds have found application in imaging methodologies [Mathis et al, 2007] and are being investigated in a number of imaging techniques, such as magnetic resonance spectroscopy, position tomography, and single-photon emission computed tomography. The selectivity of these compounds for b-sheet-containing fibers has led to the investigation of these compounds for monitoring the progression of disease in vivo and for distinguishing potential therapeutic effects.…”