Evaluation of neurodegenerative diseases with [18F]flortaucipir : comparison of visual reads with tau PET quantification and cerebrospinal fluid analysis

Contexte & objectifs: L’avènement de biomarqueurs in vivo pour la maladie d’Alzheimer a révolutionné la recherche clinique dans ce domaine. Nous avons comparé le taux de positivité pour le biomarqueur tau (statut-T) dérivé de l’interprétation visuelle des études TEP au [18F]flortaucipir (FTP), de l’analyse quantitative du FTP et de la mesure de la protéine Tau phosphorylée en position 281 (PTau181) dans le liquide céphalorachidien (LCR). Méthodologie: Nous avons inclus 351 participants avec divers diagnostics cliniques provenant de trois cohortes ayant subi une étude TEP au FTP ainsi qu’une mesure du PTau181 dans un délai de 18 mois. Le statut-T a été dérivé de : (1) l’interprétation visuelle à l’aveugle du FTP par deux observateurs; (2) la quantification SUVR (standardized uptake value ratio) du FTP d’une région d’intérêt composite temporale (seuil : SUVR ≥ 1.27) ; (3) la concentration dans le LCR de Elecsys® Phospho-Tau (181P) (Roche Diagnostics) (seuil : PTau181 ≥ 24.5 pg/ml). Résultats: L’interprétation visuelle du FTP a entraîné le plus haut taux de T+, alors que les T+ par quantification SUVR augmentaient progressivement des sujets cognitivement normaux (CN) vers les sujets avec troubles cognitifs légers (TCL) et ceux avec démence de type Alzheimer (DA). Le taux de T+ par PTau181 était intermédiaire à ceux de l’analyse visuelle et quantitative du FTP pour les CN, similaire à la quantification SUVR pour les TCL et plus faible chez les DA. La concordance entre le statut-T par paire de modalité fluctuait de 68% à 76% et variait selon le diagnostic, étant plus élevé chez les DA. L’interprétation visuelle du FTP offrait la plus haute sensibilité (0.96) pour discriminer entre les sujets avec TCL ou DA amyloïde-positifs des sujets CN et non-Alzheimer, mais une spécificité plus faible (0.60). La spécificité était la plus élevée avec la quantification SUVR (0.91) avec une sensibilité de 0.89, alors que la sensibilité (0.73) et la spécificité (0.72) étaient de même niveau pour le PTau181 dans le LCR. Conclusion: Le choix d’un biomarqueur tau pourrait varier selon le stade de la maladie et les objectifs de recherche visant à maximiser la sensibilité ou la spécificité. L’interprétation visuelle des TEP tau augmente la sensibilité en comparaison avec la quantification seule, en particulier dans les stades précoces de la maladie.Background & purpose: The advent of in vivo biomarkers for Alzheimer’s disease (AD) pathology has transformed clinical research in this field. The purpose of this study is to compare rates of tau biomarker positivity (T-status) per the 2018 AD Research Framework derived from [18F]flortaucipir (FTP) PET visual assessment, FTP quantification, and cerebrospinal fluid (CSF) phosphorylated Tau-181 (PTau181) concentration. Methods: We included 351 subjects with varying clinical diagnoses from three cohorts with available FTP PET and CSF PTau181 within 18 months. T-status was derived from: (1) FTP blinded visual assessment by two raters; (2) FTP standardized uptake value ratio (SUVR) quantification from a temporal meta-ROI (threshold: SUVR ≥ 1.27); (3) Elecsys® Phospho-Tau (181P) CSF (Roche Diagnostics) concentrations (threshold: PTau181 ≥ 24.5 pg/ml). Results: FTP visual reads yielded the highest rates of T+, while T+ by SUVR increased progressively from cognitively normal (CN) through mild cognitive impairment (MCI) and to AD dementia. T+ designation by CSF PTau181 was intermediate between FTP visual reads and SUVR values in CN, similar to SUVR in MCI, and lower in AD dementia. Concordance in T- status between modality pairs ranged from 68% to 76% and varied by clinical diagnosis, being highest in patients with AD dementia. In discriminating Aβ+ MCI and AD subjects from healthy controls and non-AD participants, FTP visual assessment was the most sensitive (0.96) but the least specific (0.60) approach. Specificity was highest with FTP SUVR (0.91) with a sensitivity of 0.89. Sensitivity (0.73) and specificity (0.72) were balanced for PTau181. Conclusion: The choice of a tau biomarker may differ by disease stage and research goals that seek to maximize sensitivity or specificity. Visual interpretations of tau PET enhance sensitivity compared to quantification alone, particularly in early disease stages

Grandparents as Foster Parents: Psychological Distress, Commitment, and Sensitivity to their Grandchildren

Grandparents are increasingly solicited to become foster parents. This study aims to describe the psychological distress, parental sensitivity, and parental commitment of a group of Quebec foster grandparents. Forty-eight foster parents were assessed in this study, including 12 grandparents. Psychological distress was assessed using the Symptom Checklist–90–R (SCL–90–R®; Derogatis & Lazarus 1994), parental sensitivity using the short version of the Maternal Behavior Q-Sort (Tarabulsy et al., 2009; Pederson & Moran, 1995) and commitment using a semi-structured interview (This is My Baby; TIMB: Bates & Dozier, 1998). Results indicate no difference between foster parents and grandparents as a function of parental characteristics, sensitivity and commitment. However, results show an association between grandparent status and depressive symptoms even after controlling for family income and child externalization. Challenges faced by foster grandparents are discussed as well as their need of support from child welfare protection

Expression of 8-oxoguanine DNA glycosylase (Ogg1) in mouse retina

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EXAFS characterization of oxaliplatin anticancer drug and its degradation in chloride media.

Oxaliplatin is a second-generation platinum-based anticancer drug. Its degradation is studied in solution, in the presence of chloride ions (in neutral or acidic media) in excess. In both cases the degradation product precipitates immediately. The EXAFS spectra of these products show that they are identical. EXAFS modeling and refinement of the first coordination sphere shows that two light atoms are replaced by two chloride ions. The complete refinement of the local structure is possible by studying the multiple-scattering signal. The results show that the main multiple-scattering contribution is due to the binding oxalato group and that the degradation product is [Cl(2)-(diaminocyclohexane)-Pt(II)]

How to assess the role of Pt and Zn in the nephrotoxicity of Pt anti-cancer drugs?: An investigation combining μXRF and statistical analysis. Part II: Clinical application

International audienceIn this contribution, an approach developed previously for mice is used for human biopsy. In the case of patient 1, Pt detection is performed 6 days after the last oxaliplatin infusion, while for patient 2, the biopsy was performed more than 15 days after his first platin infusion and several dialysis. Even for these biological samples, experiments show that synchrotron mediated mXRF is a suitable tool to detect Pt in kidney biopsy, and thus probably for any organ exposed to Pt. Therefore, mXRF could also be of major interest to decipher the mechanism beyond Pt induced neurotoxicity, ototoxicity on human biopsy. Pharmacoavailability of chemotherapies is a major concern because some treatment failures are explained by poor tumor penetration of the active molecule. mXRF could be an elegant way to map the distribution of Pt inside cancerous cells at the micrometer scale. Pt and Zn are only two of the numerous trace elements that mXRF can detect; heavy metal intoxication diagnosis and the toxicity mechanism probably could also benefit from this innovative technique

A novel antiangiogenic and vascular normalization therapy targeted against human CD160 receptor

A monoclonal anti-CD160 antibody inhibits the growth of new vessels in pathological ocular and tumor neoangiogenesis but not in healthy tissues