%0 Journal Article %J J Alzheimers Dis %D 2017 %T The Cerebrospinal Fluid Aβ1-42/Aβ1-40 Ratio Improves Concordance with Amyloid-PET for Diagnosing Alzheimer's Disease in a Clinical Setting. %A Niemantsverdriet, Ellis %A Ottoy, Julie %A Somers, Charisse %A De Roeck, Ellen %A Struyfs, Hanne %A Soetewey, Femke %A Verhaeghe, Jeroen %A Van den Bossche, Tobi %A Van Mossevelde, Sara %A Goeman, Johan %A De Deyn, Peter Paul %A Mariën, Peter %A Versijpt, Jan %A Sleegers, Kristel %A Van Broeckhoven, Christine %A Wyffels, Leonie %A Albert, Adrien %A Ceyssens, Sarah %A Stroobants, Sigrid %A Staelens, Steven %A Bjerke, Maria %A Engelborghs, Sebastiaan %X

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.

%B J Alzheimers Dis %V 60 %P 561-576 %8 2017 %G eng %N 2 %R 10.3233/JAD-170327 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Longitudinal Characterization of [18F]-FDG and [18F]-AV45 Uptake in the Double Transgenic TASTPM Mouse Model. %A Waldron, Ann-Marie %A Wyffels, Leonie %A Verhaeghe, Jeroen %A Richardson, Jill C %A Schmidt, Mark %A Stroobants, Sigrid %A Langlois, Xavier %A Staelens, Steven %X

We aimed to monitor the timing of amyloid-β deposition in relation to changes in brain function using in vivo imaging with [18F]-AV45 and [18F]-FDG in a mouse model of Alzheimer's disease. TASTPM transgenic mice and wild-type controls were scanned longitudinally with [18F]-AV45 and [18F]-FDG before (3 months of age) and at multiple time points after the onset of amyloid deposition (6, 9, 12, and 15 months of age). As expected with increasing amyloidosis, TASTPM mice demonstrated progressive age-dependent increases in [18F]-AV45 uptake that were significantly higher than for WT from 9 months onwards and correlated to ex vivo measures of amyloid burden. The metabolism of [18F]-AV45 produces several brain penetrant radiometabolites and normalization to a reference region helps to negate this non-specific binding and improve the sensitivity of [18F]-AV45. The observed trajectory of [18F]-FDG alterations deviated from our proposed hypothesis of gradual decreases with worsening amyloidosis. While [18F]-FDG uptake in TASTPM mice was significantly lower than that of WT at 9 months, reduced [18F]-FDG was not associated with aging in TASTPM mice. Moreover, [18F]-FDG uptake did not correlate to measures of ex vivo amyloid burden. Our findings suggest that while amyloid-β is sufficient to induce hypometabolism, these pathologies are not linked in a dose-dependent manner in TASTPM mice.

%B J Alzheimers Dis %V 55 %P 1537-1548 %8 2017 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/27911309?dopt=Abstract %R 10.3233/JAD-160760