Lowering β-Amyloid Levels Rescues Learning and Memory in a Down Syndrome Mouse Model
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{"title"=>"Lowering β-amyloid levels rescues learning and memory in a down syndrome mouse model", "type"=>"journal", "authors"=>[{"first_name"=>"William J.", "last_name"=>"Netzer", "scopus_author_id"=>"6602411606"}, {"first_name"=>"Craig", "last_name"=>"Powell", "scopus_author_id"=>"7402081825"}, {"first_name"=>"Yi", "last_name"=>"Nong", "scopus_author_id"=>"6602171926"}, {"first_name"=>"Jacqueline", "last_name"=>"Blundell", "scopus_author_id"=>"7103375351"}, {"first_name"=>"Lili", "last_name"=>"Wong", "scopus_author_id"=>"36453333100"}, {"first_name"=>"Karen", "last_name"=>"Duff", "scopus_author_id"=>"35393105600"}, {"first_name"=>"Marc", "last_name"=>"Flajolet", "scopus_author_id"=>"6506892777"}, {"first_name"=>"Paul", "last_name"=>"Greengard", "scopus_author_id"=>"36050698100"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"359289601", "sgr"=>"77956214742", "issn"=>"19326203", "pmid"=>"20532168", "scopus"=>"2-s2.0-77956214742", "doi"=>"10.1371/journal.pone.0010943", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)"}, "id"=>"715f481d-db2a-3fc2-bfc5-407955039132", "abstract"=>"beta-amyloid levels are elevated in Down syndrome (DS) patients throughout life and are believed to cause Alzheimer's disease (AD) in adult members of this population. However, it is not known if beta-amyloid contributes to intellectual disability in younger individuals. We used a gamma-secretase inhibitor to lower beta-amyloid levels in young mice that model DS. This treatment corrected learning deficits characteristic of these mice, suggesting that beta-amyloid-lowering therapies might improve cognitive function in young DS patients.", "link"=>"http://www.mendeley.com/research/lowering-%CE%B2amyloid-levels-rescues-learning-memory-down-syndrome-mouse-model", "reader_count"=>57, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>3, "Researcher"=>13, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>1, "Student > Master"=>8, "Other"=>3, "Student > Bachelor"=>6, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>3, "Researcher"=>13, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>1, "Student > Master"=>8, "Other"=>3, "Student > Bachelor"=>6, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>1, "Mathematics"=>1, "Medicine and Dentistry"=>10, "Agricultural and Biological Sciences"=>23, "Neuroscience"=>5, "Arts and Humanities"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>9, "Social Sciences"=>2, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Neuroscience"=>{"Neuroscience"=>5}, "Social Sciences"=>{"Social Sciences"=>2}, "Psychology"=>{"Psychology"=>9}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>23}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Colombia"=>1, "United States"=>1, "United Kingdom"=>1, "Mexico"=>1, "France"=>1, "Germany"=>1}, "group_count"=>1}

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  • {"files"=>["https://ndownloader.figshare.com/files/846174"], "description"=>"<p>DAPT was administered to Ts65Dn and control mice (100 mg/kg/day) two days prior to, and throughout, the maze testing. (A) Hidden platform test, latency to reach platform during training. (B) Probe trial on day 12, number of platform crossings. (C) Visible platform test, latency to reach platform. (D) Thigmotaxis. Statistical Analysis: n = 6 for all groups (A–D). (A) 2-way ANOVA with repeated measures revealed a main effect of genotype F1,20 = 11.31, p = 0.003 & Day F10,200 = 4.90, p = 3.00E-06 and an interaction between genotype and DAPT F1,20 = 7.73, p = 0.012. Post-hoc planned comparison test between Ts65Dn+vehicle and all 3 other groups (Ts65Dn+vehicle vs. Ts65Dn+DAPT p = 0.02, Ts65Dn+vehicle vs. control+vehicle p = 0.0003, Ts65Dn+vehicle vs. control+DAPT p = 0.008, n = 6 in all groups for all figures). (B) 2-way ANOVA for number of target platform crossings revealed an interaction between genotype and DAPT F1,20 = 8.46, p = 0.009. Post-hoc planned comparison test revealed a significant difference between Ts65Dn+vehicle vs. Ts65Dn+DAPT p = 0.01 and between Ts65Dn+vehicle vs. control+vehicle p = 0.007. No significant differences were observed for number of crossings of the analogous, virtual opposite platform location (not shown). (C) 2-way ANOVA with repeated measures revealed significant effects of genotype, F1,20 = 9.91, p = 0.005 and day, F10,200 = 21.42, p = 0.001, as well as a significant interaction between genotype and DAPT, F1,20 = 5.43, p = 0.03. Post-hoc planned comparison test revealed significant differences between Ts65Dn+vehicle vs. all 3 other groups (vs. Ts65Dn+DAPT p = 0.04, vs. control+vehicle p = 0.003, and vs. control+DAPT p = 0.005). (D) 2-way ANOVA with repeated measures revealed main effects of genotype, F1,20 = 5.13, p = 0.03 & day F10,200 = 21.94, p<1.00E-06 with an interaction between genotype and DAPT, F1,20 = 5.43, p = 0.03. Post-hoc planned comparison test revealed only a significant difference between Ts65Dn+vehicle vs. control+vehicle p = 0.004.</p>", "links"=>[], "tags"=>["reverses", "deficits", "4-month-old", "ts65dn", "mice", "morris"], "article_id"=>516621, "categories"=>["Biochemistry", "Neuroscience", "Genetics"], "users"=>["William J. Netzer", "Craig Powell", "Yi Nong", "Jacqueline Blundell", "Lili Wong", "Karen Duff", "Marc Flajolet", "Paul Greengard"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010943.g002", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DAPT_reverses_cognitive_deficits_in_4_month_old_Ts65Dn_mice_in_the_Morris_water_maze_/516621", "title"=>"DAPT reverses cognitive deficits in 4-month-old Ts65Dn mice in the Morris water maze.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:05:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/846072"], "description"=>"<p>Four-month-old Ts65Dn mice and wild type colony mate controls were treated with vehicle or DAPT (100 mg/kg/day) for 4 days. (A) Representative western blots of APP, CTFs and β-actin from control (ctrl) and Ts65Dn (Ts) mice. (B) Left panel, quantification of APP (Students t-test, mean±s.e.m.,unpaired, two-tailed, n = 8 per group). Ctrl+Vehicle vs. Ts+Vehicle, p = 0.0003; Ctrl+DAPT vs. Ts+DAPT, p = 0.0002; Ctrl+Vehicle vs. Ts+DAPT, p = 0.0001; Ctrl+DAPT vs. Ts+Vehicle, p = 0.0006. Right panel, combined (C99, C89 and C83) CTFs (all means differ significantly, n = 8, 1-way ANOVA, p = 0.0002; significant differences between individual pairs of mean calculated by Students t-test, mean±s.e.m., unpaired, two-tailed). (C) Aβ40 and Aβ42 quantification from control and Ts65Dn mice. Left panel, Aβ40 (Students t-test, mean±s.e.m., unpaired, two-tailed, n = 6 per group); Ctrl+Vehicle vs. Ts+Vehicle, p = 0.0173; Ctrl+Vehicle vs. Ctrl+DAPT, p = 0.0043; Ctrl+DAPT vs. Ts+Vehicle, p = 0.0079; Ts+Vehicle vs. Ts+DAPT, p = 0.0082. Right panel, Aβ42 (Students t-test, mean±s.e.m., unpaired, two-tailed, n = 6 per group); Ctrl+Vehicle vs. Ts+Vehicle, p = 0.0169; Ctrl+DAPT vs. Ts+Vehicle, p = 0.0003; Ts+Vehicle vs. Ts+DAPT, p = 0.0052.</p>", "links"=>[], "tags"=>["raises", "app-ctf", "levels", "lowers", "brains", "4-month-old", "ts65dn"], "article_id"=>516510, "categories"=>["Biochemistry", "Neuroscience", "Genetics"], "users"=>["William J. Netzer", "Craig Powell", "Yi Nong", "Jacqueline Blundell", "Lili Wong", "Karen Duff", "Marc Flajolet", "Paul Greengard"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010943.g001", "stats"=>{"downloads"=>3, "page_views"=>233, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DAPT_raises_APP_CTF_levels_and_lowers_A_946_levels_in_brains_of_4_month_old_Ts65Dn_mice_/516510", "title"=>"DAPT raises APP-CTF levels and lowers Aβ levels in brains of 4-month-old Ts65Dn mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:04:59"}

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