Affiliations: [a] Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia | [b] Department of Medicine, Austin Health, Heidelberg, VIC, Australia | [c] The Mental Health Research Institute of Victoria, Parkville, VIC, Australia
Correspondence:
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Correspondence to: Victor L. Villemagne, MD, Department of Nuclear Medicine and Centre for PET, Austin Health, 145 Studley Rd, Heidelberg, VIC 3084, Australia. Tel.: +61 3 9496 3321; Fax: +61 3 9458 5663; E-mail: villemagne@petnm.unimelb.edu.au.
Abstract: The introduction of radiotracers for the non-invasive in vivo quantification of amyloid-β (Aβ) burden in the brain has revolutionized the approach to the evaluation of Alzheimer's disease (AD). Aβ burden as measured by positron emission tomography (PET) matches histopathological reports of Aβ distribution in aging and dementia. It appears more accurate than FDG for the diagnosis of AD, and is an excellent aid in the differential diagnosis of AD from frontotemporal lobar degeneration. Apolipoprotein E ε4 carriers, independent of diagnosis or disease severity, present with higher Aβ burden than non-ε4 carriers. As new therapies enter clinical trials, the role of Aβ imaging in vivo is becoming increasingly crucial. Aβ imaging allows the in vivo assessment of brain Aβ pathology and its changes over time, providing highly accurate, reliable, and reproducible quantitative statements of regional or global Aβ burden in the brain, essential for therapeutic trial recruitment and for the evaluation of anti-Aβ treatments. Although Aβ burden as assessed by PET does not strongly correlate with cognitive impairment in AD, it does correlate with memory impairment and a higher risk for cognitive decline in the aging population and mild cognitive impairment (MCI) subjects. This correlation with memory impairment, one of the earliest symptoms of AD, suggests that Aβ deposition is not part of normal aging, supporting the hypothesis that Aβ deposition occurs well before the onset of symptoms and likely represents preclinical AD in asymptomatic individuals and prodromal AD in MCI. Further longitudinal observations, coupled with different disease-specific biomarkers to assess potential downstream effects of Aβ, are required to confirm this hypothesis and further elucidate the role of Aβ deposition in the course of AD.
