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Cerebrospinal Fluid Levels of Amyloid Beta 1-43 Mirror 1-42 in Relation to Imaging Biomarkers of Alzheimer’s Disease

Introduction: Amyloid beta 1-43 (Aβ43), with its additional C-terminal threonine residue, is hypothesized to play a role in early Alzheimer’s disease pathology possibly different from that of amyloid beta 1-42 (Aβ42). Cerebrospinal fluid (CSF) Aβ43 has been suggested as a potential novel biomarker f...

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Autores principales: Almdahl, Ina S., Lauridsen, Camilla, Selnes, Per, Kalheim, Lisa F., Coello, Christopher, Gajdzik, Beata, Møller, Ina, Wettergreen, Marianne, Grambaite, Ramune, Bjørnerud, Atle, Bråthen, Geir, Sando, Sigrid B., White, Linda R., Fladby, Tormod
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293760/
https://www.ncbi.nlm.nih.gov/pubmed/28223932
http://dx.doi.org/10.3389/fnagi.2017.00009
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author Almdahl, Ina S.
Lauridsen, Camilla
Selnes, Per
Kalheim, Lisa F.
Coello, Christopher
Gajdzik, Beata
Møller, Ina
Wettergreen, Marianne
Grambaite, Ramune
Bjørnerud, Atle
Bråthen, Geir
Sando, Sigrid B.
White, Linda R.
Fladby, Tormod
author_facet Almdahl, Ina S.
Lauridsen, Camilla
Selnes, Per
Kalheim, Lisa F.
Coello, Christopher
Gajdzik, Beata
Møller, Ina
Wettergreen, Marianne
Grambaite, Ramune
Bjørnerud, Atle
Bråthen, Geir
Sando, Sigrid B.
White, Linda R.
Fladby, Tormod
author_sort Almdahl, Ina S.
collection PubMed
description Introduction: Amyloid beta 1-43 (Aβ43), with its additional C-terminal threonine residue, is hypothesized to play a role in early Alzheimer’s disease pathology possibly different from that of amyloid beta 1-42 (Aβ42). Cerebrospinal fluid (CSF) Aβ43 has been suggested as a potential novel biomarker for predicting conversion from mild cognitive impairment (MCI) to dementia in Alzheimer’s disease. However, the relationship between CSF Aβ43 and established imaging biomarkers of Alzheimer’s disease has never been assessed. Materials and Methods: In this observational study, CSF Aβ43 was measured with ELISA in 89 subjects; 34 with subjective cognitive decline (SCD), 51 with MCI, and four with resolution of previous cognitive complaints. All subjects underwent structural MRI; 40 subjects on a 3T and 50 on a 1.5T scanner. Forty subjects, including 24 with SCD and 12 with MCI, underwent (18)F-Flutemetamol PET. Seventy-eight subjects were assessed with (18)F-fluorodeoxyglucose PET (21 SCD/7 MCI and 11 SCD/39 MCI on two different scanners). Ten subjects with SCD and 39 with MCI also underwent diffusion tensor imaging. Results: Cerebrospinal fluid Aβ43 was both alone and together with p-tau a significant predictor of the distinction between SCD and MCI. There was a marked difference in CSF Aβ43 between subjects with (18)F-Flutemetamol PET scans visually interpreted as negative (37 pg/ml, n = 27) and positive (15 pg/ml, n = 9), p < 0.001. Both CSF Aβ43 and Aβ42 were negatively correlated with standardized uptake value ratios for all analyzed regions; CSF Aβ43 average rho -0.73, Aβ42 -0.74. Both CSF Aβ peptides correlated significantly with hippocampal volume, inferior parietal and frontal cortical thickness and axial diffusivity in the corticospinal tract. There was a trend toward CSF Aβ42 being better correlated with cortical glucose metabolism. None of the studied correlations between CSF Aβ43/42 and imaging biomarkers were significantly different for the two Aβ peptides when controlling for multiple testing. Conclusion: Cerebrospinal fluid Aβ43 appears to be strongly correlated with cerebral amyloid deposits in the same way as Aβ42, even in non-demented patients with only subjective cognitive complaints. Regarding imaging biomarkers, there is no evidence from the present study that CSF Aβ43 performs better than the classical CSF biomarker Aβ42 for distinguishing SCD and MCI.
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spelling pubmed-52937602017-02-21 Cerebrospinal Fluid Levels of Amyloid Beta 1-43 Mirror 1-42 in Relation to Imaging Biomarkers of Alzheimer’s Disease Almdahl, Ina S. Lauridsen, Camilla Selnes, Per Kalheim, Lisa F. Coello, Christopher Gajdzik, Beata Møller, Ina Wettergreen, Marianne Grambaite, Ramune Bjørnerud, Atle Bråthen, Geir Sando, Sigrid B. White, Linda R. Fladby, Tormod Front Aging Neurosci Neuroscience Introduction: Amyloid beta 1-43 (Aβ43), with its additional C-terminal threonine residue, is hypothesized to play a role in early Alzheimer’s disease pathology possibly different from that of amyloid beta 1-42 (Aβ42). Cerebrospinal fluid (CSF) Aβ43 has been suggested as a potential novel biomarker for predicting conversion from mild cognitive impairment (MCI) to dementia in Alzheimer’s disease. However, the relationship between CSF Aβ43 and established imaging biomarkers of Alzheimer’s disease has never been assessed. Materials and Methods: In this observational study, CSF Aβ43 was measured with ELISA in 89 subjects; 34 with subjective cognitive decline (SCD), 51 with MCI, and four with resolution of previous cognitive complaints. All subjects underwent structural MRI; 40 subjects on a 3T and 50 on a 1.5T scanner. Forty subjects, including 24 with SCD and 12 with MCI, underwent (18)F-Flutemetamol PET. Seventy-eight subjects were assessed with (18)F-fluorodeoxyglucose PET (21 SCD/7 MCI and 11 SCD/39 MCI on two different scanners). Ten subjects with SCD and 39 with MCI also underwent diffusion tensor imaging. Results: Cerebrospinal fluid Aβ43 was both alone and together with p-tau a significant predictor of the distinction between SCD and MCI. There was a marked difference in CSF Aβ43 between subjects with (18)F-Flutemetamol PET scans visually interpreted as negative (37 pg/ml, n = 27) and positive (15 pg/ml, n = 9), p < 0.001. Both CSF Aβ43 and Aβ42 were negatively correlated with standardized uptake value ratios for all analyzed regions; CSF Aβ43 average rho -0.73, Aβ42 -0.74. Both CSF Aβ peptides correlated significantly with hippocampal volume, inferior parietal and frontal cortical thickness and axial diffusivity in the corticospinal tract. There was a trend toward CSF Aβ42 being better correlated with cortical glucose metabolism. None of the studied correlations between CSF Aβ43/42 and imaging biomarkers were significantly different for the two Aβ peptides when controlling for multiple testing. Conclusion: Cerebrospinal fluid Aβ43 appears to be strongly correlated with cerebral amyloid deposits in the same way as Aβ42, even in non-demented patients with only subjective cognitive complaints. Regarding imaging biomarkers, there is no evidence from the present study that CSF Aβ43 performs better than the classical CSF biomarker Aβ42 for distinguishing SCD and MCI. Frontiers Media S.A. 2017-02-07 /pmc/articles/PMC5293760/ /pubmed/28223932 http://dx.doi.org/10.3389/fnagi.2017.00009 Text en Copyright © 2017 Almdahl, Lauridsen, Selnes, Kalheim, Coello, Gajdzik, Møller, Wettergreen, Grambaite, Bjørnerud, Bråthen, Sando, White and Fladby. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Almdahl, Ina S.
Lauridsen, Camilla
Selnes, Per
Kalheim, Lisa F.
Coello, Christopher
Gajdzik, Beata
Møller, Ina
Wettergreen, Marianne
Grambaite, Ramune
Bjørnerud, Atle
Bråthen, Geir
Sando, Sigrid B.
White, Linda R.
Fladby, Tormod
Cerebrospinal Fluid Levels of Amyloid Beta 1-43 Mirror 1-42 in Relation to Imaging Biomarkers of Alzheimer’s Disease
title Cerebrospinal Fluid Levels of Amyloid Beta 1-43 Mirror 1-42 in Relation to Imaging Biomarkers of Alzheimer’s Disease
title_full Cerebrospinal Fluid Levels of Amyloid Beta 1-43 Mirror 1-42 in Relation to Imaging Biomarkers of Alzheimer’s Disease
title_fullStr Cerebrospinal Fluid Levels of Amyloid Beta 1-43 Mirror 1-42 in Relation to Imaging Biomarkers of Alzheimer’s Disease
title_full_unstemmed Cerebrospinal Fluid Levels of Amyloid Beta 1-43 Mirror 1-42 in Relation to Imaging Biomarkers of Alzheimer’s Disease
title_short Cerebrospinal Fluid Levels of Amyloid Beta 1-43 Mirror 1-42 in Relation to Imaging Biomarkers of Alzheimer’s Disease
title_sort cerebrospinal fluid levels of amyloid beta 1-43 mirror 1-42 in relation to imaging biomarkers of alzheimer’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293760/
https://www.ncbi.nlm.nih.gov/pubmed/28223932
http://dx.doi.org/10.3389/fnagi.2017.00009
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