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P1‐015: PROTEIN KINASE ACTIVITY DECREASES WITH BRAAK STAGE IN HIPPOCAMPAL POSTMORTEM BRAIN TISSUE AS REVEALED BY USING A PEPTIDE‐BASED MICROARRAY PLATFORM
Author(s) -
Rosenberger Andrea,
Hilhorst Riet,
Hoozemans Jeroen,
Flier Wiesje M.,
Rozemuller Annemieke,
Scheltens Philip,
Vies Saskia M.
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.2014.05.250
Subject(s) - kinase , signal transduction , phosphorylation , biology , protein kinase a , protein kinase c , microbiology and biotechnology , map2k7 , protein phosphorylation , tyrosine kinase , biochemistry , cyclin dependent kinase 2
tissue. Methods: Frozen brain tissue from healthy controls (HCs) and neuropathologically confirmed cases of AD (CERAD criteria) were obtained from the Douglas-Bell Canada Brain Bank (Douglas Mental Health University Institute, Montreal, Canada). In total, 26 samples from the hippocampus (HIPP) (HC1⁄419, AD1⁄47), 18 from the prefrontal cortex (PFC) (HC1⁄414, AD1⁄44), 20 from the posterior cingulate cortex (PCC) (HC 1⁄4 11, AD 1⁄4 9) and 22 from the inferior parietal cortex (IPC) (HC1⁄415, A1⁄47)were included.[18 F]T807 autoradiography (specific activity, > 71,000 mCi/micromol) was carried out following 2.5-hour incubation of frozen tissue slices (20 mm thick). Imaging plates were scanned using BAS5000 Phosphoimager (Fuji-Film), with total binding obtained for all regions of interest. Results: No significant differences between control and AD groups were noted in terms of sex distribution, age and postmortem delay (P < 0.05). Binding of [18 F]T807 was significantly higher in AD tissue, as compared to CN [HIPP (P < 0.01), PFC (P < 0.01), IPC (P < 0.05), PCC (P < 0.05], with the magnitude of difference highest in the IPC. Conclusions: [18 F]T807 successfully differentiated CN and AD post-mortem tissue, with binding substantially higher in AD, particularly in the IPC. Our findings support the current perspective on [18 F]T807 as a promising tau molecular imaging agent.

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