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

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: Ellis Niemantsverdriet, Julie Ottoy, Charisse Somers, Ellen De Roeck, Hanne Struyfs, Femke Soetewey, Jeroen Verhaeghe, Tobi Van den Bossche, Sara Van Mossevelde, Johan Goeman, Peter Paul De Deyn, Peter Mariën, Jan Versijpt, Kristel Sleegers, Christine Van Broeckhoven, Leonie Wyffels, Adrien Albert, Sarah Ceyssens, Sigrid Stroobants, Steven Staelens, Maria Bjerke, Sebastiaan Engelborghs
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 60 Issue 2 Pg. 561-576 ( 2017) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 28869470 (Publication Type: Journal Article)

Chemical References

• Amyloid beta-Peptides
• Aniline Compounds
• Ethylene Glycols
• Peptide Fragments
• amyloid beta-protein (1-40)
• amyloid beta-protein (1-42)
• tau Proteins
• florbetapir

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (cerebrospinal fluid, diagnostic imaging)
• Amyloid beta-Peptides (cerebrospinal fluid)
• Aniline Compounds (metabolism)
• Cognitive Dysfunction (cerebrospinal fluid, diagnostic imaging)
• Ethylene Glycols (metabolism)
• Female
• Humans
• Imaging, Three-Dimensional
• Longitudinal Studies
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Neuropsychological Tests
• Peptide Fragments (cerebrospinal fluid)
• Positron-Emission Tomography
• Psychiatric Status Rating Scales
• tau Proteins (cerebrospinal fluid)