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[IC‐P‐192]: PRECLINICAL CHARACTERIZATION OF PI‐2620, A NOVEL TAU PET TRACER FOR DETECTION OF TAU IN AD AND OTHER TAUOPATHIES
Author(s) -
Mueller Andre,
Kroth Heiko,
Schieferstein Hanno,
Berndt Mathias,
Oden Felix,
Capotosti Francesca,
Molette Jerome,
Juergens Tanja,
Darmency Vincent,
SchmittWillich Heribert,
Hickman David,
Tamagnan Gilles,
Pfeifer Andrea,
Dinkelborg Ludger,
Muhs Andreas,
Stephens Andrew
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.2017.06.2567
Subject(s) - human brain , chemistry , tau protein , tau pathology , dementia , pittsburgh compound b , tauopathy , amyloid (mycology) , binding selectivity , neuroscience , alzheimer's disease , biochemistry , biology , pathology , medicine , disease , neurodegeneration , inorganic chemistry
Background: In this multi-modal study, we investigated the topography and inter-relationships of in vivo tau, perfusion and cortical thinning in mild cognitive impairment (MCI) and Alzheimer’s disease (AD).Methods:13 controls, 18MCI and 11AD subjects underwent T1-MPRAGE and PET imaging with the tau ligand [F]-AV1451. Atrophy was measured from MRI and the simplified reference tissue model (SRTM) was applied to the [F]-AV-1451 PET data to quantify both tau deposition (binding; BPND) and perfusion (relative to the cerebellum; R1). T1 data were processed with Freesurfer 6 beta to derive cortical thickness maps. PET data were coregistered to the T1 and sampled onto the cortical surface (Greve et al., 2014) (Figure 1). Zscore maps of tau, hypoperfusion and atrophy were derived for each subject with reference against the healthy controls. Surface-based comparisons of tau, perfusion, and atrophy were compared between the groups. Paired T-Tests were used to compare the global Z score of each marker, and correlations across the brain regions were performed to assess the inter-relationship among tau, hypoperfusion and cortical thickness. Results:There was a striking overlap of tau deposition, hypoperfusion and cortical thinning in the AD group (Figure 2). Relative to healthy controls, the AD group showed a widespread increase in tau, together with an overlapping but more restricted pattern of hypoperfusion and cortical thinning in temporo-parietal cortices (Figure 3). The three markers of pathology were highly inter-correlated in AD (Figure 4). Tau Z (3.0 61.4) significantly exceeded both atrophy Z (0.8 6 0.7, p < 0.001) and hypoperfusion Z (0.4 6 0.5, p<0.001) (Figure 5). MCI showed increased tau in the left inferior temporal cortex compared to healthy controls. In MCI, tau Z was significantly correlated with atrophy Z (r 1⁄4 0.4, p 1⁄4 0.002), but tau Z was similar compared to atrophy Z. Conclusions: The wider extent and greater severity of tau relative to atrophy and hypoperfusion provide preliminary in vivo evidence to support a model in which tau pathology precedes neurodegeneration in AD. This hierarchy was not observed in theMCI group, andmay suggest an acceleration of tau during the progression from MCI to AD.