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P1‐241: A NOVEL RADIOLIGAND FOR ASSESSING BACE OCCUPANCY IN P‐GP KO MOUSE BRAIN
Author(s) -
Zeng Zhizhen,
Miller Patricia,
O'Malley Stacey,
Stauffer Shaun,
Stachel Shawn,
Bennacef Idriss,
Hostetler Eric,
Sur Cyrille,
Williamson David
Publication year - 2014
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.2014.05.480
Subject(s) - radioligand , in vivo , chemistry , pharmacology , knockout mouse , enzyme , in vitro , amyloid (mycology) , binding site , amyloid precursor protein , microbiology and biotechnology , biochemistry , alzheimer's disease , receptor , medicine , biology , disease , inorganic chemistry
a parametric deconvolution (Mouridsen et al., 2011). Capillary dysfunction was evaluated as a single parameter, the transit time coefficient of variation: TTCV 1⁄4 CTH/MTT. The TTCV maps were parcellated using the T1w images and an atlas-based method (Fonov et al., 2011). Hippocampal atrophy was estimated by automatically calculating the hippocampal volume (Coup e et al., 2012)from the T1w images. Perfusion parameters and hippocampal volumes were correlated with MMSE scores within the patient group using a linear model.Results:Hippocampal volumewas significantly smaller in AD patients (left: p1⁄40.010, right: p1⁄40.009) compared to controls (Figure 1). Within patients, the left hippocampal volume was closely correlated to MMSE (p<0.001), while the right hippocampal volume was not correlated (p1⁄40.136). Capillary dysfunction as measured by TTCV was significantly (p<0.05) negatively correlated with MMSE in all major lobes, basal ganglia and thalamus, while this was not the case in the cerebellum (Figure 2). Conclusions: Our finding of transit time coefficient of variation correlated with MMSE is consistent with the capillary dysfunction hypothesis of AD and suggests that MRI perfusion measures of capillary flow heterogeneity is a potential new imaging biomarker in AD. Further studies should address the causal relation between capillary dysfunction, neurodegeneration and atrophy.