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Estimation of amylo...
Estimation of amyloid distribution by F-18 flutemetamol PET predicts the neuropathological phase of amyloid beta-protein deposition
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Thal, D. R. (författare)
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Beach, T. G. (författare)
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Zanette, M. (författare)
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visa fler...
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Lilja, J. (författare)
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- Heurling, Kerstin (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Chakrabarty, A. (författare)
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Ismail, A. (författare)
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Farrar, G. (författare)
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Buckley, C. (författare)
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Smith, A. P. L. (författare)
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(creator_code:org_t)
- 2018-08-19
- 2018
- Engelska.
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 136:4, s. 557-567
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https://link.springe...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The deposition of the amyloid β-protein (Aβ) in senile plaques is one of the histopathological hallmarks of Alzheimer’s disease (AD). Aβ-plaques arise first in neocortical areas and, then, expand into further brain regions in a process described by 5 phases. Since it is possible to identify amyloid pathology with radioactive-labeled tracers by positron emission tomography (PET) the question arises whether it is possible to distinguish the neuropathological Aβ-phases with amyloid PET imaging. To address this question we reassessed 97 cases of the end-of-life study cohort of the phase 3 [18F]flutemetamol trial (ClinicalTrials.gov identifiers NCT01165554, and NCT02090855) by combining the standardized uptake value ratios (SUVRs) with pons as reference region for cortical and caudate nucleus-related [18F]flutemetamol-retention. We tested them for their prediction of the neuropathological pattern found at autopsy. By defining threshold levels for cortical and caudate nucleus SUVRs we could distinguish different levels of [18F]flutemetamol uptake termed PET-Aβ phase estimates. When comparing these PET-Aβ phase estimates with the neuropathological Aβ-phases we found that PET-Aβ phase estimate 0 corresponded with Aβ-phases 0-2, 1 with Aβ-phase 3, 2 with Aβ-phase 4, and 3 with Aβ-phase 5. Classification using the PET-Aβ phase estimates predicted the correct Aβ-phase in 72.16% of the cases studied here. Bootstrap analysis was used to confirm the robustness of the estimates around this association. When allowing a range of±1 phase for a given Aβ-phase correct classification was given in 96.91% of the cases. In doing so, we provide a novel method to convert SUVR-levels into PET-Aβ phase estimates that can be easily translated into neuropathological phases of Aβ-deposition. This method allows direct conclusions about the pathological distribution of amyloid plaques (Aβ-phases) in vivo. Accordingly, this method may be ideally suited to detect early preclinical AD-patients, to follow them with disease progression, and to provide a more precise prognosis for them based on the knowledge about the underlying pathological phase of the disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Amyloid β-protein
- Neuropathological staging
- Amyloid PET
- Imaging
- [18F]Flutemetamol
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Thal, D. R.
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Beach, T. G.
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Zanette, M.
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Lilja, J.
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Heurling, Kersti ...
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Chakrabarty, A.
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visa fler...
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Ismail, A.
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Farrar, G.
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Buckley, C.
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Smith, A. P. L.
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Neurovetenskaper
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Acta Neuropathol ...
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Göteborgs universitet