Specialized biomarkers: Use of amyloid-PET imaging

Figure: Amyloid-PET imaging in Alzheimer’s disease: Examples of amyloid-negative (left) and amyloid-positive (right) positron emission tomography (PET) scans.⁵ In this figure, the amyloid-PET ligand [¹⁸F]AZD4694 is shown.⁵ The hotter colors indicate more amyloid-PET tracer binding, and colder colours indicate low amyloid-PET tracer binding.⁵ The prototypical amyloid-positive PET pattern is of elevated amyloid in the brain’s posterior cingulate cortex, prefrontal cortex, as well as lateral parietal and temporal cortices.⁵ These regions display minimal tracer uptake in the amyloid-negative case (left), who has low binding across the whole cerebral cortex.⁵ Finally, it is important to note that amyloid-PET tracers have some binding to white matter, which explains the small amounts of hotter colours in the amyloid-negative case.⁵ More information on amyloid-PET visual reads can be found in Johnson KA, Minoshima S, Bohnen NI, et al. Alzheimers Dement. 2013;54(3):476-490.⁵

Amyloid-PET uses standardized tracer-specific visual reading procedures and has documented high reproducibility across PET centres.² As a neuroimaging technique, it allows non-invasive, in vivo detection of amyloid plaques, one of the key pathological characteristics of AD.² The prototypical amyloid-positive PET pattern is of elevated amyloid in the brain’s posterior cingulate cortex, prefrontal cortex, as well as lateral parietal and temporal cortices.⁵ These regions display minimal tracer uptake with low binding across the whole cerebral cortex in patients that are amyloid negative.⁵ Amyloid-PET can also allow the identification of amyloid pathology in clinically atypical variants of AD including posterior cortical atrophy, frontal-executive variant, or the logopenic variant,^2,6,7 however, it does not provide the ability to distinguish between distinct amyloid-positive disorders which may show similar patterns of amyloid deposition.² It should be noted that amyloid-PET tracers have some binding to white matter, resulting in small amounts of hotter colours observed on tracers in amyloid-negative cases.⁵

When comparing the ability of different modalities to predict progression to AD, a slightly higher sensitivity has been reported for amyloid-PET over [¹⁸F]FDG-PET.⁸ However, [¹⁸F]FDG-PET demonstrates a higher specificity and accuracy for predicting short-term progression.^8,9 [¹⁸F]FDG-PET has reached the most advanced phase of validation compared with other PET markers and amyloid imaging has almost achieved analytical and clinical validity.¹⁰

References:
1.La Joie R, Ayakta N, Seeley WW, et al. Multisite study of the relationships between antemortem [¹¹C]PIB-PET Centiloid values and postmortem measures of Alzheimer’s disease neuropathology. Alzheimers Dement 2019; 15 (2): 205–216.

2.Chételat G, Arbizu J, Barthel H, et al. Amyloid-PET and ¹⁸F-FDG-PET in the diagnostic investigation of Alzheimer’s disease and other dementias. Lancet Neurol 2020; 19 (11): 951–962.

3.Johnson KA, Minoshima S, Bohnen NI, et al. Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association. Alzheimers Dement 2013; 9 (1): e1–16.

4.Cummings J. Anti-amyloid monoclonal antibodies are transformative treatments that redefine Alzheimer’s disease therapeutics. Drugs 2023; 83 (7): 569–576.

5.Therriault J. Biomarkers for the in vivo diagnosis of Alzheimer’s disease. Available at: https://neurotorium.org/biomarkers-for-the-in-vivo-diagnosis-of-alzheimers-disease/. Accessed 15 November 2023.

6.Bergeron D, Gorno-Tempini ML, Rabinovici GD, et al. Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia. Ann Neurol 2018; 84 (5): 729–740.

7.Dickerson BC, McGinnis SM, Xia C, et al. Approach to atypical Alzheimer’s disease and case studies of the major subtypes. CNS Spectr 2017; 22 (6): 439-449.

8.Mallik A, Drzezga A, Minoshima S. Clinical amyloid imaging. Semin Nucl Med 2017; 47 (1): 31–43.

9.Blazhenets G, Ma Y, Sörensen A, et al; Alzheimer Disease Neuroimaging Initiative. Predictive value of ¹⁸F-Florbetapir and ¹⁸F-FDG PET for conversion from mild cognitive impairment to Alzheimer dementia. J Nucl Med 2020; 61 (4): 597–603.

10.Frisoni GB, Boccardi M, Barkhof F, et al. Strategic roadmap for an early diagnosis of Alzheimer’s disease based on biomarkers. Lancet Neurol 2017; 16 (8): 661–676.