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The Cerebrospinal Fluid Aβ1-42/Aβ1-40 Ratio Improves Concordance with Amyloid-PET for Diagnosing Alzheimer's Disease in a Clinical Setting.
J Alzheimers Dis 2017; 60(2):561-576JA

Abstract

BACKGROUND

Evidence suggests that the concordance between amyloid-PET and cerebrospinal fluid (CSF) amyloid-β (Aβ) increases when the CSF Aβ1-42/Aβ1-40 ratio is used as compared to CSF Aβ1-42 levels alone.

OBJECTIVE

In order to test this hypothesis, we set up a prospective longitudinal study comparing the concordance between different amyloid biomarkers for Alzheimer's disease (AD) in a clinical setting.

METHODS

Seventy-eight subjects (AD dementia (n = 17), mild cognitive impairment (MCI, n = 48), and cognitively healthy controls (n = 13)) underwent a [18F]Florbetapir ([18F]AV45) PET scan, [18F]FDG PET scan, MRI scan, and an extensive neuropsychological examination. In a large subset (n = 67), a lumbar puncture was performed and AD biomarkers were analyzed (Aβ1-42, Aβ1-40, T-tau, P-tau181).

RESULTS

We detected an increased concordance in the visual and quantitative (standardized uptake value ratio (SUVR) and total volume of distribution (VT)) [18F]AV45 PET measures when the CSF Aβ1-42/Aβ1-40 was applied compared to Aβ1-42 alone. CSF biomarkers were stronger associated to [18F]AV45 PET for SUVR values when considering the total brain white matter as reference region instead of cerebellar grey matterConclusions:The concordance between CSF Aβ and [18F]AV45 PET increases when the CSF Aβ1-42/Aβ1-40 ratio is applied. This finding is of most importance for the biomarker-based diagnosis of AD as well as for selection of subjects for clinical trials with potential disease-modifying therapies for AD.

Authors+Show Affiliations

Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, UAntwerp, Antwerp, Belgium.Molecular Imaging Center Antwerp (MICA), UAntwerp, Antwerp, Belgium.Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, UAntwerp, Antwerp, Belgium.Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, UAntwerp, Antwerp, Belgium. Faculty of Psychology and Educational Sciences, Vrije Universiteit Brussels, Brussels, Belgium.Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, UAntwerp, Antwerp, Belgium.Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, UAntwerp, Antwerp, Belgium.Molecular Imaging Center Antwerp (MICA), UAntwerp, Antwerp, Belgium.VIB-UAntwerp Center for Molecular Neurology, Antwerp, Belgium. Laboratory of Neurogenetics, Institute Born-Bunge, UAntwerp, Antwerp, Belgium. Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.VIB-UAntwerp Center for Molecular Neurology, Antwerp, Belgium. Laboratory of Neurogenetics, Institute Born-Bunge, UAntwerp, Antwerp, Belgium. Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, UAntwerp, Antwerp, Belgium. Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium. Clinical and Experimental Neurolinguistics, CLIN, Vrije Universiteit Brussel (VUB), Brussels, Belgium.Vrije Universiteit Brussel(VUB), University Hospital Brussels (UZ Brussel), Department of Neurology, Brussels, Belgium.VIB-UAntwerp Center for Molecular Neurology, Antwerp, Belgium. Laboratory of Neurogenetics, Institute Born-Bunge, UAntwerp, Antwerp, Belgium.VIB-UAntwerp Center for Molecular Neurology, Antwerp, Belgium. Laboratory of Neurogenetics, Institute Born-Bunge, UAntwerp, Antwerp, Belgium.Molecular Imaging Center Antwerp (MICA), UAntwerp, Antwerp, Belgium. Departmentof Nuclear Medicine, Antwerp University Hospital, Antwerp, Belgium.Departmentof Nuclear Medicine, Antwerp University Hospital, Antwerp, Belgium.Departmentof Nuclear Medicine, Antwerp University Hospital, Antwerp, Belgium.Molecular Imaging Center Antwerp (MICA), UAntwerp, Antwerp, Belgium. Departmentof Nuclear Medicine, Antwerp University Hospital, Antwerp, Belgium.Molecular Imaging Center Antwerp (MICA), UAntwerp, Antwerp, Belgium.Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, UAntwerp, Antwerp, Belgium.Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, UAntwerp, Antwerp, Belgium. Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28869470

Citation

Niemantsverdriet, Ellis, et al. "The Cerebrospinal Fluid Aβ1-42/Aβ1-40 Ratio Improves Concordance With Amyloid-PET for Diagnosing Alzheimer's Disease in a Clinical Setting." Journal of Alzheimer's Disease : JAD, vol. 60, no. 2, 2017, pp. 561-576.
Niemantsverdriet E, Ottoy J, Somers C, et al. The Cerebrospinal Fluid Aβ1-42/Aβ1-40 Ratio Improves Concordance with Amyloid-PET for Diagnosing Alzheimer's Disease in a Clinical Setting. J Alzheimers Dis. 2017;60(2):561-576.
Niemantsverdriet, E., Ottoy, J., Somers, C., De Roeck, E., Struyfs, H., Soetewey, F., ... Engelborghs, S. (2017). The Cerebrospinal Fluid Aβ1-42/Aβ1-40 Ratio Improves Concordance with Amyloid-PET for Diagnosing Alzheimer's Disease in a Clinical Setting. Journal of Alzheimer's Disease : JAD, 60(2), pp. 561-576. doi:10.3233/JAD-170327.
Niemantsverdriet E, et al. The Cerebrospinal Fluid Aβ1-42/Aβ1-40 Ratio Improves Concordance With Amyloid-PET for Diagnosing Alzheimer's Disease in a Clinical Setting. J Alzheimers Dis. 2017;60(2):561-576. PubMed PMID: 28869470.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Cerebrospinal Fluid Aβ1-42/Aβ1-40 Ratio Improves Concordance with Amyloid-PET for Diagnosing Alzheimer's Disease in a Clinical Setting. AU - Niemantsverdriet,Ellis, AU - Ottoy,Julie, AU - Somers,Charisse, AU - De Roeck,Ellen, AU - Struyfs,Hanne, AU - Soetewey,Femke, AU - Verhaeghe,Jeroen, AU - Van den Bossche,Tobi, AU - Van Mossevelde,Sara, AU - Goeman,Johan, AU - De Deyn,Peter Paul, AU - Mariën,Peter, AU - Versijpt,Jan, AU - Sleegers,Kristel, AU - Van Broeckhoven,Christine, AU - Wyffels,Leonie, AU - Albert,Adrien, AU - Ceyssens,Sarah, AU - Stroobants,Sigrid, AU - Staelens,Steven, AU - Bjerke,Maria, AU - Engelborghs,Sebastiaan, PY - 2017/9/5/pubmed PY - 2018/4/10/medline PY - 2017/9/5/entrez KW - Aβ1–42/Aβ1–40 ratio KW - [18F]Florbetapir ([18F]AV45) KW - amyloid KW - amyloid imaging KW - biomarkers KW - cerebrospinal fluid KW - magnetic resonance imaging SP - 561 EP - 576 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 60 IS - 2 N2 - BACKGROUND: Evidence suggests that the concordance between amyloid-PET and cerebrospinal fluid (CSF) amyloid-β (Aβ) increases when the CSF Aβ1-42/Aβ1-40 ratio is used as compared to CSF Aβ1-42 levels alone. OBJECTIVE: In order to test this hypothesis, we set up a prospective longitudinal study comparing the concordance between different amyloid biomarkers for Alzheimer's disease (AD) in a clinical setting. METHODS: Seventy-eight subjects (AD dementia (n = 17), mild cognitive impairment (MCI, n = 48), and cognitively healthy controls (n = 13)) underwent a [18F]Florbetapir ([18F]AV45) PET scan, [18F]FDG PET scan, MRI scan, and an extensive neuropsychological examination. In a large subset (n = 67), a lumbar puncture was performed and AD biomarkers were analyzed (Aβ1-42, Aβ1-40, T-tau, P-tau181). RESULTS: We detected an increased concordance in the visual and quantitative (standardized uptake value ratio (SUVR) and total volume of distribution (VT)) [18F]AV45 PET measures when the CSF Aβ1-42/Aβ1-40 was applied compared to Aβ1-42 alone. CSF biomarkers were stronger associated to [18F]AV45 PET for SUVR values when considering the total brain white matter as reference region instead of cerebellar grey matterConclusions:The concordance between CSF Aβ and [18F]AV45 PET increases when the CSF Aβ1-42/Aβ1-40 ratio is applied. This finding is of most importance for the biomarker-based diagnosis of AD as well as for selection of subjects for clinical trials with potential disease-modifying therapies for AD. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/28869470/The_Cerebrospinal_Fluid_Aβ1_42/Aβ1_40_Ratio_Improves_Concordance_with_Amyloid_PET_for_Diagnosing_Alzheimer's_Disease_in_a_Clinical_Setting_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-170327 DB - PRIME DP - Unbound Medicine ER -