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P4‐012: An RNAI screen for genes that modify human amyloid induced paralysis in caenorhabditis elegans facilitates functional analysis of candidate risk factors for Alzheimer's disease
Author(s) -
M. Moloney Aileen,
Fraboulet Sandrine,
Link Christopher D.,
Williams Julie,
Lomas David A.,
Crowther Damian,
Sattelle David B.
Publication year - 2009
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.2009.04.882
Subject(s) - caenorhabditis elegans , biology , gene , rna interference , model organism , genetics , transgene , genome wide association study , disease , drosophila melanogaster , computational biology , single nucleotide polymorphism , medicine , rna , genotype , pathology
promoting neurofibrillary pathology. Methods: In order to investigate the neuroprotective effects of Cerebrolysin on TAU pathology, a new model for neurofibrillary alterations was developed using somatic gene transfer with AAV2-mutTAU (P301L). The Thy1-mutant APP tg mice (3 m/o) received bilateral injections of AAV2-mutTAU or AAV-GFP, into the hippocampus. Results: After 3 months, compared to non-tg controls, in APP tg mice intra-hippocampal injections with AAV2-mutTAU resulted in localized increased accumulation of phosphorylated TAU and neurodegeneration. Compared with vehicle-treated controls, treatment with Cerebrolysin (3 months at 5ml/kg) resulted in a significant decrease in the levels of TAU phosphorylation at critical sites dependent on GSK3b and CDK5 activity in APP tg injected with AAV2-mutTAU. This was accompanied by amelioration of the neurodegenerative alterations in the hippocampus. Conclusions: This study supports the concept that Cerebrolysin neuroprotective effects might evolve reducing the phosphorylation of TAU at critical sites.