A new frontier for amyloid PET imaging: multiple sclerosis

Morbelli, Silvia; Bauckneht, Matteo; Capitanio, Selene; Pardini, Matteo; Roccatagliata, Luca; Nobili, Flavio

doi:10.1007/s00259-018-4232-8

Cited by 10 publications

(9 citation statements)

References 29 publications

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“…Our findings indicate that, in an elderly cohort spanning the entire AD continuum and, to a lesser extent, in non-AD amnestic patients, low FBP retention in the WM was associated with (1) MRI markers of WM degeneration, (2) abnormal AD fluid biomarkers, and (3) increased risk of progressive cognitive decline in early-stage AD. Taken together, our findings add to a growing body of literature linking WM abnormalities in multiple sclerosis and aging with reduced colocalized Aβ PET tracer uptake [19][20][21][22][23][24][25][26][27][28][29] and further highlight the importance of demyelination, assessed with FBP PET, as a marker of disease progression at both preclinical and prodromal stages of AD.…”

Section: Discussionsupporting

confidence: 69%

“…Supported by recent investigations, Aβ PET has been recently repurposed as a marker of myelin integrity in cerebral WM [19][20][21][22][23][24][25][26]. Although the binding mechanism is currently not fully understood, the elevated WM signal observed with Aβ PET tracers might be explained by the affinity of the later for the beta-sheet structure displayed by the myelin basic protein [27].…”

Section: Introductionmentioning

confidence: 99%

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18F-florbetapir PET as a marker of myelin integrity across the Alzheimer’s disease spectrum

Moscoso

Silva‐Rodríguez²,

Aldrey

et al. 2021

Eur J Nucl Med Mol Imaging

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Purpose Recent evidence suggests that PET imaging with amyloid-β (Aβ) tracers can be used to assess myelin integrity in cerebral white matter (WM). Alzheimer’s disease (AD) is characterized by myelin changes that are believed to occur early in the disease course. Nevertheless, the extent to which demyelination, as measured with Aβ PET, contributes to AD progression remains unexplored. Methods Participants with concurrent 18F-florbetapir (FBP) PET, MRI, and cerebrospinal fluid (CSF) examinations were included (241 cognitively normal, 347 Aβ-positive cognitively impaired, and 207 Aβ-negative cognitively impaired subjects). A subset of these participants had also available diffusion tensor imaging (DTI) images (n = 195). We investigated cross-sectional associations of FBP retention in the white matter (WM) with MRI-based markers of WM degeneration, AD clinical progression, and fluid biomarkers. In longitudinal analyses, we used linear mixed models to assess whether FBP retention in normal-appearing WM (NAWM) predicted progression of WM hyperintensity (WMH) burden and clinical decline. Results In AD-continuum individuals, FBP retention in NAWM was (1) higher compared with WMH regions, (2) associated with DTI-based measures of WM integrity, and (3) associated with longitudinal progression of WMH burden. FBP uptake in WM decreased across the AD continuum and with increasingly abnormal CSF biomarkers of AD. Furthermore, FBP retention in the WM was associated with large-calibre axon degeneration as reflected by abnormal plasma neurofilament light chain levels. Low FBP uptake in NAWM predicted clinical decline in preclinical and prodromal AD, independent of demographics, global cortical Aβ, and WMH burden. Most of these associations were also observed in Aβ-negative cognitively impaired individuals. Conclusion These results support the hypothesis that FBP retention in the WM is myelin-related. Demyelination levels progressed across the AD continuum and were associated with clinical progression at early stages, suggesting that this pathologic process might be a relevant degenerative feature in the disease course.

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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

18F-florbetapir PET as a marker of myelin integrity across the Alzheimer’s disease spectrum

Moscoso

Silva‐Rodríguez²,

Aldrey

et al. 2021

Eur J Nucl Med Mol Imaging

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show abstract

“…Taken together, our ndings add to a growing body of literature linking WM abnormalities in Multiple Sclerosis and aging with reduced colocalized Aβ PET tracer uptake [19][20][21][22][23][24][25][26][27][28][29] and further highlights the importance of demyelination, assessed with FBP PET, as a marker of disease progression at both preclinical and prodromal stages of AD.…”

Section: Discussionsupporting

confidence: 59%

“…Supported by recent investigations, Aβ PET has been recently repurposed as a marker of myelin integrity in cerebral WM [19][20][21][22][23][24][25][26]. Although the binding mechanism is currently not fully understood, the elevated WM signal observed with Aβ PET tracers might be explained by the a nity of the later for the beta-sheet structure displayed by the myelin basic protein [27].…”

Section: Introductionmentioning

confidence: 99%

18F-florbetapir PET as a marker of myelin integrity across the Alzheimer’s disease spectrum

Moscoso¹,

Silva‐Rodríguez²,

Aldrey³

et al. 2021

Preprint

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Purpose: Recent evidence suggest that PET imaging with amyloid-β (Aβ) tracers can be used to assess myelin integrity in cerebral white matter (WM). Alzheimer’s disease (AD) is characterized by myelin changes that are believed to occur early in the disease course. Nevertheless, the extent to which demyelination, as measured with Aβ PET, contributes to AD progression remains unexplored.Methods: Participants with concurrent 18F-florbetapir (FBP), MRI, and cerebrospinal fluid (CSF) examinations were included (241 cognitively normal, 347 Aβ-positive cognitively impaired, and 207 Aβ-negative cognitively impaired subjects). A subset of these participants had also available diffusion tensor imaging (DTI) images (n=195). We investigated cross-sectional associations of FBP retention in the white matter (WM) with MRI-based markers of WM degeneration, AD clinical progression, and CSF biomarkers. In longitudinal analyses, we used linear mixed models to assess whether FBP retention in normal-appearing WM (NAWM) predicted progression of WM hyperintensity (WMH) burden and clinical decline. Results: In AD-continuum individuals, FBP retention in NAWM was 1) higher compared to WMH regions, 2) associated with DTI-based measures of WM integrity, and 3) associated with longitudinal progression of WMH burden. FBP uptake in WM decreased across the AD continuum and with increasingly abnormal CSF biomarkers of AD. Furthermore, FBP retention in the WM was associated with large-calibre axon degeneration as reflected by abnormal plasma neurofilament light chain levels. Low FBP uptake in NAWM predicted clinical decline in preclinical and prodromal AD, independent of demographics, global cortical Aβ, and WMH burden. Most of these associations were also observed in Aβ-negative cognitively impaired individuals.Conclusion: These results support the hypothesis that FBP retention in the WM is myelin-dependent. Demyelination levels progressed across the AD continuum and were associated with clinical progression at early stages, suggesting that this pathologic process might be a relevant degenerative feature in the disease course.

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“…Recently, PET with amyloid tracers, an emerging tool to image amyloid deposition in neurodegenerative diseases, has also been suggested as a potential marker of WM damage in MS (Chandra 2015; Morbelli et al 2019). All amyloid PET tracers bind to the WM, independently of the presence or absence of beta-amyloid deposition in the adjacent GM (Morbelli and Bauckneht 2018).…”

Section: Pet Tracers For Myelin Kineticsmentioning

confidence: 99%

Molecular imaging of multiple sclerosis: from the clinical demand to novel radiotracers

Bauckneht

Capitanio

Raffa

et al. 2019

EJNMMI radiopharm. chem.

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Background Brain PET imaging with different tracers is mainly clinically used in the field of neurodegenerative diseases and brain tumors. In recent years, the potential usefulness of PET has also gained attention in the field of MS. In fact, MS is a complex disease and several processes can be selected as a target for PET imaging. The use of PET with several different tracers has been mainly evaluated in the research setting to investigate disease pathophysiology (i.e. phenotypes, monitoring of progression) or to explore its use a surrogate end-point in clinical trials. Results We have reviewed PET imaging studies in MS in humans and animal models. Tracers have been grouped according to their pathophysiological targets (ie. tracers for myelin kinetic, neuroinflammation, and neurodegeneration). The emerging clinical indication for brain PET imaging in the differential diagnosis of suspected tumefactive demyelinated plaques as well as the clinical potential provided by PET images in view of the recent introduction of PET/MR technology are also addressed. Conclusion While several preclinical and fewer clinical studies have shown results, full-scale clinical development programs are needed to translate molecular imaging technologies into a clinical reality that could ideally fit into current precision medicine perspectives.

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A new frontier for amyloid PET imaging: multiple sclerosis

Cited by 10 publications

References 29 publications

18F-florbetapir PET as a marker of myelin integrity across the Alzheimer’s disease spectrum

18F-florbetapir PET as a marker of myelin integrity across the Alzheimer’s disease spectrum

18F-florbetapir PET as a marker of myelin integrity across the Alzheimer’s disease spectrum

Molecular imaging of multiple sclerosis: from the clinical demand to novel radiotracers

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