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O1‐10‐05: CATHEPSIN B KNOCKOUT REDUCES PGLU‐ABETA AND ABETA, AND IMPROVES MEMORY DEFICITS, IN THE APPLON MOUSE MODEL OF AD
Author(s) -
Hook Vivian,
Yu Jin,
Toneff Thomas,
Kindy Mark Stephen,
Hook Greg
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.2014.04.114
Subject(s) - knockout mouse , endocrinology , amyloid precursor protein , chemistry , amyloid (mycology) , amyloid beta , medicine , gene knockout , cathepsin b , microbiology and biotechnology , alzheimer's disease , peptide , biology , biochemistry , gene , enzyme , disease , inorganic chemistry
acquired 30-60 min p.i. using 12 MBq of tracer while data analyses consisted of VOI-based cortical standard-uptake-value-ratio (SUVR) analyses, including partial volume effect correction. Results: A total of 128 microPET recordings were acquired. Baseline results revealed elevated SUVR of 1.04 6 0.08 in the APP-Swe treatment group compared to their vehicle controls (0.98 6 0.05; p1⁄40.07). At 16 months follow-up SUVR in GSMtreated APP-Swemice remained nearly constant while the APP-Swe vehicle group showed a slightly increasing signal compared to baseline (+2.1% vs. +4.7%; p1⁄40.39). At 18months GSM-treated APP-Swemice again remained constant whereas the vehicle group showed a marked increase (+1.2% vs. +12.7%; p<0.01). WT mice remained constant over time. Conclusions: This is the first amyloid-PET monitored long-lasting GSM treatment study in a transgenic AD model. GSM treatment could prevent amyloidogenesis compared to vehicle. The strength of PET lies in the non-invasive possibility of assessing individual plaque-load kinetics and therefore enabling coping with inter-animal variations.