A review of β-amyloid neuroimaging in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is the most common cause of dementia worldwide. As advancing age is the greatest risk factor for developing AD, the number of those afflicted is expected to increase markedly with the aging of the world's population. The inability to definitively diagnose AD until autopsy remains an impediment to establishing effective targeted treatments. Neuroimaging has enabled in vivo visualization of pathological changes in the brain associated with the disease, providing a greater understanding of its pathophysiological development and progression. However, neuroimaging biomarkers do not yet offer clear advantages over current clinical diagnostic criteria for them to be accepted into routine clinical use. Nonetheless, current insights from neuroimaging combined with the elucidation of biochemical and molecular processes in AD are informing the ongoing development of new imaging techniques and their application. Much of this research has been greatly assisted by the availability of transgenic mouse models of AD. In this review we summarize the main efforts of neuroimaging in AD in humans and in mouse models, with a specific focus on β-amyloid, and discuss the potential of new applications and novel approaches.

Keywords: Alzheimer's disease; CT; MRI; PET; biomarkers; mouse models; neuroimaging.

Figure 1

Hypothetical model of various neuroimaging biomarkers and their predicted utility during disease progression. Adapted from Ewers et al. (2011) and Frisoni et al. (2010).

Figure 2

(A) [11C]-PIB-PET images illustrating amyloid depositions in brains of an AD patient (axial view) and different strains of APP transgenic or PS-1/APP double transgenic mice (coronal view) merged onto anatomical MRI maps. Human and mouse images are differently scaled according to the maximal binding potential for the radiotracer in each species, as indicated by vertical bars from Higuchi et al. (2010). (B) Five-way anatomic spatial coregistration of a 24-month-old APP/PS1 AD transgenic mouse brain. Ex vivo MRI scans of matched sections imaged using either a (A) T₂SE or (D) T^*₂ GE pulse sequence. Matched adjacent histological sections processed with (G) DAB-enhanced iron staining, (J) thioflavine S amyloid staining, or (M) anti-Aβ peptide immunohistochemistry. Scale bar = 500 μm. (B,E,H,K,N) Higher magnification of hippocampal plaques positively matched by spatial coregistration. Corresponding plaques are labeled with numbers when present in a particular section. (C,F,I,L,O) Higher magnification of thalamic plaques positively matched by spatial coregistration. (O) Scale bar = 100 μm from Wengenack et al. (2011).