Amyloid PET imaging: applications beyond Alzheimer's disease

Abstract

As a biomarker of beta-amyloid, positron emission tomography (PET) amyloid imaging offers a unique opportunity to detect the presence of this protein in the human body during life. Besides Alzheimer's disease (AD), deposits of beta-amyloid in the brain are also present in other neurodegenerative diseases associated to dementia, such as Parkinson's disease and dementia with Lewy bodies, as well as in other processes affecting brain function, such as cerebral amyloid angiopathy, brain trauma, Down's syndrome and meningiomas, as shown by post-mortem pathology studies. Furthermore, in systemic amyloidosis other organs besides the brain are affected, and amyloid PET imaging may be suitable for the identification of these extra-cerebral amyloid depositions. Finally, the potential use of amyloid PET tracer accumulation in cerebral white matter (WM) as a marker of myelin is being investigated, leading to some promising results in patients with WM lesions and multiple sclerosis. In this article, a review of the ongoing research pointing to a broader application of amyloid PET imaging in clinical practice beyond AD is provided.

Keywords: Amyloid PET; Brain trauma; Cardiac amyloidosis; Cerebral amyloid angiopathy; Down’s syndrome; Multiple sclerosis.

Fig. 1

Representative ¹⁸F-florbetaben PET transaxial images overlaid on individual coregistered MR images of a healthy control (HC) and patients with Parkinson’s disease (PD), dementia with Lewy bodies (DLB), mild cognitive impairment (MCI), Alzheimer’s disease (AD), frontotemporal lobar degeneration (FTLD), and vascular dementia (VaD). Only the DLB, MCI and AD patients show cortical ¹⁸F-florbetaben uptake in addition to the non-specific white matter uptake visible in negative scans of HC, PD, FTLD, and VaD. The cortical tracer uptake in DLB is lower than in AD. All images are scaled to same SUVR maximum. This research was originally published in JNM. Villemagne et al. [11] © by the Society of Nuclear Medicine and Molecular Imaging, Inc

Fig. 2

Representative ¹¹C-PIB PET images at two transaxial levels from normal control (NC) (¹¹C-PIB-negative), Alzheimer’s disease (AD), and cerebral amyloid angiopathy (CAA) subjects. Compared with AD and NC, CAA subjects had an intermediate level of global ¹¹C-PIB retention, but compared with AD, had relatively increased occipital retention. Microbleeds seen in this patient, shown in coregistered gradient echo magnetic resonance images, at times appear proximal to foci of amyloid deposition (small arrows). Reproduced from Ann Neurol, Johnson et al. [34] ©2007 with permission from the American Neurological Association

Fig. 3

¹¹C-PIB distribution volume ratio (DVR) maps from a control and three patients scanned at different times after TBI. Note the progressive decrease in ¹¹C-PIB uptake as time after TBI increases. Reproduced from JAMA Neurol, Hong YT et al. (doi:10.1001/jamaneurol.2013.4847) with permission from American Medical Association

Fig. 4

¹⁸F-florbetaben SUVR versus age in young cognitively normal healthy controls (n = 70; SUVR = 0.001 × age + 1.173, R ² = −0.01) (left graph) (Piramal Imaging, unpublished data) and subjects with Down’s syndrome (n = 39; SUVR = 0.030 × age + 0.045, R ² = 0.39) (middle graph). A graph showing the percentage of positive ¹⁸F-florbetaben scans grouped by age clusters is shown in the right hand side

Fig. 5

Short-axis images of ¹¹C-PIB retention index (RI) and myocardial blood flow (MBF) in (left to right) patients with high, intermediate, and partially increased ¹¹C-PIB retention and a healthy control. Liver is clearly visible in ¹¹C-PIB images of one patient (second column images) patient and healthy control, and is just outside PET field of view for other two patients. Liver uptake is due to biliary excretion of ¹¹C-PIB and is likely not related to amyloid binding. This research was originally published in JNM. Antoni et al. [78] © by the Society of Nuclear Medicine and Molecular Imaging, Inc

Fig. 6

MP-RAGE 3T MRI (a, d, f) and corresponding co-registered ¹¹C-PIB slices (b, c, e, g) from two representative patients from Stankoff et al. [83] (d–g correspond to the same patient). c Shows superposition of MRI and PET images. Arrows point to MA plaques, and arrowheads point to gray matter structures, both appearing as a loss of uptake on PET images. Reproduced from Ann Neurol, Stankoff et al. [83] with permission from the American Neurological Association