Imaging Alzheimer's disease pathophysiology with PET

Schilling, Lucas Porcello; Zimmer, Eduardo R.; Shin, Monica; Leuzy, Antoine; Pascoal, Tharick A.; Borelli, Wyllians Vendramini; Palmini, André; Gauthier, Serge; Rosa‐Neto, Pedro

doi:10.1590/s1980-5764-2016dn1002003

Cited by 40 publications

(25 citation statements)

References 147 publications

(211 reference statements)

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“…Unfortunately, PiB does not label Aβ deposits in some mouse models, including both APP/PS1 and Tg2576 (Klunk et al, ; Snellman et al, ), but at least one quantitative comparison between amyloid PET and methoxy‐X04 labeling in different mouse lines has been performed (Brendel et al, ). The significance of the differential affinity of imaging probes for various forms of Aβ is still an active area of research (Schilling et al, ).…”

Section: Discussionmentioning

confidence: 99%

Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer's disease

Whitesell

Buckley

Knox

et al. 2018

J of Comparative Neurology

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A variety of Alzheimer's disease (AD) mouse models overexpress mutant forms of human amyloid precursor protein (APP), producing high levels of amyloid β (Aβ) and forming plaques. However, the degree to which these models mimic spatiotemporal patterns of Aβ deposition in brains of AD patients is unknown. Here, we mapped the spatial distribution of Aβ plaques across age in three APP-overexpression mouse lines (APP/PS1, Tg2576, and hAPP-J20) using in vivo labeling with methoxy-X04, high throughput whole brain imaging, and an automated informatics pipeline. Images were acquired with high resolution serial two-photon tomography and labeled plaques were detected using custom-built segmentation algorithms. Image series were registered to the Allen Mouse Brain Common Coordinate Framework, a 3D reference atlas, enabling automated brain-wide quantification of plaque density, number, and location. In both APP/PS1 and Tg2576 mice, plaques were identified first in isocortex, followed by olfactory, hippocampal, and cortical subplate areas. In hAPP-J20 mice, plaque density was highest in hippocampal areas, followed by isocortex, with little to no involvement of olfactory or cortical subplate areas.Within the major brain divisions, distinct regions were identified with high (or low) plaque accumulation; for example, the lateral visual area within the isocortex of APP/PS1 mice had relatively higher plaque density compared with other cortical areas, while in hAPP-J20 mice, plaques were densest in the ventral retrosplenial cortex. In summary, we show how whole brain imaging of amyloid pathology in mice reveals the extent to which a given model recapitulates the regional Aβ deposition patterns described in AD.

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Section: Discussionmentioning

confidence: 99%

Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer's disease

Whitesell

Buckley

Knox

et al. 2018

J of Comparative Neurology

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“…A recent investigation indicated that an important dose-response effect reflects the association between amyloid burden and cognitive decline (Farrell et al, 2017), which suggests that the rate of accumulation is a better predictor of cognitive decline than a single threshold. Besides, it is known that cognitive decline is strongly associated with Tau deposition (Aschenbrenner et al, 2018;Braak et al, 2006;Schilling et al, 2016). Hence, further studies assessing longitudinal amyloid and tau deposition in SuperAgers may help elucidate this mechanism.…”

Section: Discussionmentioning

confidence: 99%

Neural correlates of exceptional memory ability in SuperAgers: A multimodal approach using FDG-PET, PIB-PET, and MRI

Borelli

Leal-Conceição

Andrade

et al. 2019

Preprint

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Individuals at 80 years of age or above with exceptional memory are considered SuperAgers (SA). A multimodal brain analysis of SA may provide biomarkers of successful cognitive aging. Herein, a molecular (PET-FDG, PET-PIB), functional (fMRI) and structural analysis (MRI) of SA was conducted. Ten SA, ten age-matched older adults (C80) and ten cognitively normal middle-aged adults underwent cognitive testing and neuroimaging examinations. The relationship between cognitive scores and cingulate areas and hippocampus were examined. The SA group showed increased FDG SUVr in the left subgenual Anterior Cingulate Cortex (sACC, p<0.005) as compared to that in the C80 group. The SA group also presented decreased connectivity between left sACC and posterior cingulate (p<0.005) as compared to that of C80 group. Amyloid deposition was similar between SuperAgers and control groups in the described regions or overall areas (p>0.05). These results support the key role of ACC in SA, even in the presence of amyloid deposition. It also suggests that sACC can be used as a potential memory biomarker in older adults.Brain glucose metabolism SA group showed significantly increased metabolic activity in sub-regions of the Anterior Cingulate Cortex (ACC), especially the left subgenual ACC (sACC, Table 2), as compared to that in C80 group.The right pre-subgenual region of the ACC (pACC) showed increased brain activity in SA as compared to that in C80 group; however, this relation was later corrected for multiple comparisons (1.02 ±0.08 vs. 0.88 ±0.07, p < 0.01 uncorrected) and did not survive long. Subsequently, sACC and pACC were grouped in a single ROI named ventral anterior cingulate (vACC, Fig. 1 Sup. Material).The SA group showed increased FDG SUVr for both, right and left hippocampal regions as compared to the C80 group (Table 2) but not with C50 group (p > 0.05). These tests did not pass corrections for multiple comparisons.

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“…), making early diagnostic screening as well as routine monitoring by these tools difficult (Loane & Politis ; Schilling et al . ). Instead, biomarkers based on differential expression of DNA (Ziegler et al .…”

Section: Biomarkers For Ad and Pdmentioning

confidence: 97%

Mass spectrometry: A platform for biomarker discovery and validation for Alzheimer's and Parkinson's diseases

Cilento

Jin

Stewart

et al. 2019

Journal of Neurochemistry

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Imaging Alzheimer's disease pathophysiology with PET

Cited by 40 publications

References 147 publications

Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer's disease

Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer's disease

Neural correlates of exceptional memory ability in SuperAgers: A multimodal approach using FDG-PET, PIB-PET, and MRI

Mass spectrometry: A platform for biomarker discovery and validation for Alzheimer's and Parkinson's diseases

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