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O1‐06‐06: In vivo Tau‐PET indicates expansion of tau pathology within the default mode network in Alzheimer's disease
Author(s) -
Seemiller Joseph,
Tahmasian Masoud,
Yakushev Igor,
Drzezga Alexander
Publication year - 2015
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.2015.07.062
Subject(s) - default mode network , posterior cingulate , tau pathology , voxel , neuroscience , alzheimer's disease , resting state fmri , precuneus , pathology , psychology , chemistry , functional connectivity , medicine , disease , cortex (anatomy) , functional magnetic resonance imaging , radiology
Background:We recently demonstrated the ability of lentiviral vectors encoding Tau proteins to generate genetic models of tauopathies in rodents. These data supported the development of a nonhuman primate model offering additional opportunities for the validation of imaging and biochemical biomarkers and the exploration of innovative therapies.Methods:14 adult maleMacaca fascicularis received bilateral stereotaxic injections of AAV vectors and overexpressing either the wild-type hTau1N4R (n1⁄45), the hTau1N4R P301Lmutated form of Tau (n1⁄45) or a null GFP (n1⁄44) into the hippocampus (CA1). CSF and plasma samples were collected at 3, 5, 7 and 12 months post-injection (pi.). All animals underwent F-FDG and F-DPA714 PET imaging (FOCUS220, Siemens) 10-12 months after viral injection. Animals were sacrificed at 3 or 12 months pi. Results:Both constructs are able to drive neurodegenerative process throughout the brain with the progressive appearance of tangles in the hippocampus. Tau was found hyper and abnormally phosphorylated (AT8 and MC)1 immunoreactivities) at the injection site 3 months post-delivery and a progressive neurodegenerative process occurred also in connected areas. By PET, both Glucose metabolism and neuroinflammation are modified. Peripheral biomarkers are under analysis but inflammatory ones show some changes. Conclusions: This model of tauopathy holds great promise for further investigation of diagnostic and therapeutic strategies in non-human primates. Supported by Fondation Plan Alzheimer & LabEx DISTALZ.