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J Alzheimers Dis. 2017;60(2):561-576. doi: 10.3233/JAD-170327.

The Cerebrospinal Fluid Aβ1-42/Aβ1-40 Ratio Improves Concordance with Amyloid-PET for Diagnosing Alzheimer's Disease in a Clinical Setting.

Author information

1
Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, UAntwerp, Antwerp, Belgium.
2
Molecular Imaging Center Antwerp (MICA), UAntwerp, Antwerp, Belgium.
3
Faculty of Psychology and Educational Sciences, Vrije Universiteit Brussels, Brussels, Belgium.
4
VIB-UAntwerp Center for Molecular Neurology, Antwerp, Belgium.
5
Laboratory of Neurogenetics, Institute Born-Bunge, UAntwerp, Antwerp, Belgium.
6
Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
7
Clinical and Experimental Neurolinguistics, CLIN, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
8
Vrije Universiteit Brussel(VUB), University Hospital Brussels (UZ Brussel), Department of Neurology, Brussels, Belgium.
9
Departmentof Nuclear Medicine, Antwerp University Hospital, Antwerp, Belgium.

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.

KEYWORDS:

Aβ1–42/Aβ1–40 ratio; [18F]Florbetapir ([18F]AV45); amyloid; amyloid imaging; biomarkers; cerebrospinal fluid; magnetic resonance imaging

PMID:
28869470
PMCID:
PMC5611891
DOI:
10.3233/JAD-170327
[Indexed for MEDLINE]
Free PMC Article

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