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[P4–408]: A MONOCLONAL ANTI‐OLIGOMER IGM CROSSES THE BBB AND PRODUCES COGNITIVE RESCUE BY LOWERING OLIGOMERIC FORMS OF BOTH TAU AND Aβ IN AN AD ANIMAL MODEL
Author(s) -
Goni Fernando,
Herline Krystal,
MartaAriza Mitchell,
Boutajangout Allal,
Mehta Pankaj D.,
Prelli Frances,
Wisniewski Thomas
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.07.568
Subject(s) - blood–brain barrier , saline , immunohistochemistry , monoclonal antibody , pathology , medicine , pathological , chemistry , pharmacology , antibody , immunology , central nervous system
the bias can vary across brain regions and patient groups due to variability in the time point at which TrEq (tTrEq) occurs. We investigated the tTrEq of [ F]AV-1451 across different regions and their impact on simplified quantification approaches. Methods: Six patients with probable Alzheimer’s disease (AD) (64.8 6 14.7y) and four cognitively healthy elderly (75.0 6 3.8y) underwent structural MRI and [F]AV-1451 dynamic PET scanning over 0-60, 80-140 and 160-180 min post injection together with arterial blood sampling. Tissue radioactivity (CT) curves were generated using the Harvard-Oxford atlas, with non-displaceable binding (CND) represented by the cerebellar cortex. Radioactivity concentration of specifically bound ligand was estimated as CS1⁄4CT-CND, with tTrEq determined as dCS/dt1⁄40. Arterial input Logan binding potentials (BPND1⁄4VT/VND-1) were used as reference for comparison of different time windows in the estimation of specific binding ratios (SBR1⁄4! CS dt/! CNDdt, i.e. SUVR-1). A range of time windows was examined, including the commonly used interval of 80-100 min post injection. Results:The average tTrEqdiffered between diagnostic groups and brain regions, ranging from 32.5 in the basal ganglia to 137.5 min post injection in occipital and lateral parietal cortex. Later time windows resulted in increasingly overestimated binding in AD patients using SBR, of different magnitude across regions. Conclusions: The tTrEq varies across regions, affecting the agreement between BPND and SBR differentially in different brain regions. Though Logan BPND may itself introduce a negative bias, our findings suggest that there is a regional component to the accuracy of late scan SBR, and they should thus be interpreted with caution when compared across brain regions.