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P1‐059: Cystatin B deletion in a mouse model of Alzheimer's disease, TgCRND8, ameliorates both autophagic‐lysosomal and amyloid pathologies
Author(s) -
Yang Dun-Sheng,
Stavrides Philip,
Mohan Panaiyur,
Kumar Asok,
Schmidt Stephen D.,
Pawlik Monika,
Bandyopadhyay Urmi,
Mathews Paul M.,
Levy Efrat,
Cuervo Ana M.,
Nixon Ralph A.
Publication year - 2008
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.2008.05.645
Subject(s) - autophagy , neurodegeneration , cathepsin , cathepsin b , lysosome , microbiology and biotechnology , cathepsin d , amyloid precursor protein , calpain , sequestosome 1 , alzheimer's disease , chemistry , amyloid (mycology) , proteases , biochemistry , proteasome , biology , apoptosis , medicine , disease , enzyme , inorganic chemistry
(11-12 months) and elderly (16-18 months) offspring. Following an assessment of neuromuscular function using the SHIRPA protocol, the spatial reference memories of these mice were tested using the Morris water maze. The protocol consisted of 3 days visible platform training, followed by 9 days hidden platform training. Probe trials, where the platform was removed and the mice were left to swim for 1min, were conducted on days 4, 7 and 10 of the hidden platform training. Mouse performance was recorded and assessed using the Ethovision analysis package. Results: X11 overexpression did not alter cognitive function as single transgenic X11 mice performed similarly to wild-type littermates in all age groups. In contrast, and consistent with previous reports, elderly APPswe mice performed significantly worse than their wild-type littermates, displaying increased latency to platform (p 0.026), and reduced memory retention as assessed using probe trials (p 0.950 target vs. opposite quadrant, day 10). Interestingly, APPswe/X11 double transgenic mice performed significantly better than their APPswe single transgenic littermates, displaying latencies (p 0.031, APPswe/X11 vs. APPswe) and memory retention (p 0.001, target vs. opposite quadrant, day 10) similar to those seen in their wild-type littermates. A similar result was observed in the middleaged cohort: APPswe mice displayed reduced memory retention (p 0.177 target vs. opposite quadrant, day 10), while their APPswe/X11 double transgenic littermates displayed retention (p 0.003, target vs. opposite quadrant, day 10) comparable to wild-type mice (p 0.001 target vs. opposite quadrant, day 10). Young mice displayed no memory deficiencies, regardless of genotype (p 0.001 target vs opposite quadrant, day 10). Conclusions: These data suggest that overexpression of X11 , in addition to decreasing the cerebral A load, reduces cognitive impairment in middle-aged and elderly Tg2576 mice.