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Since BDNF plays a critical role in neuronal survival, synaptic plasticity, and memory, BDNF reduction may contribute to synaptic and cellular loss and memory deficits characteristic of AD.<jats:italic>In vitro<\/jats:italic>evidence suggests that amyloid-\u03b2 (A\u03b2) contributes to BDNF downregulation in AD, but the specific A\u03b2 aggregation state responsible for this downregulation<jats:italic>in vivo<\/jats:italic>is unknown. In the present study, we examined cortical levels of BDNF mRNA in three different transgenic AD mouse models harboring mutations in<jats:italic>APP<\/jats:italic>resulting in A\u03b2 overproduction, and in a genetic mouse model of Down syndrome. Two of the three A\u03b2 transgenic strains (<jats:italic>APP<jats:sup>NLh<\/jats:sup><\/jats:italic>and TgCRND8) exhibited significantly decreased cortical BDNF mRNA levels compared with wild-type mice, whereas neither the other strain (APP<jats:sup>swe<\/jats:sup>\/PS-1) nor the Down syndrome mouse model (Ts65Dn) was affected. Only<jats:italic>APP<jats:sup>NLh<\/jats:sup><\/jats:italic>and TgCRND8 mice expressed high A\u03b2<jats:sub>42<\/jats:sub>\/A\u03b2<jats:sub>40<\/jats:sub>ratios and larger SDS-stable A\u03b2 oligomers (\u223c115 kDa). TgCRND8 mice exhibited downregulation of BDNF transcripts III and IV; transcript IV is also downregulated in AD. Furthermore, in all transgenic mouse strains, there was a correlation between levels of large oligomers, A\u03b2<jats:sub>42<\/jats:sub>\/A\u03b2<jats:sub>40<\/jats:sub>, and severity of BDNF decrease. These data show that the amount and species of A\u03b2 vary among transgenic mouse models of AD and are negatively correlated with BDNF levels. These findings also suggest that the effect of A\u03b2 on decreased BDNF expression is specific to the aggregation state of A\u03b2 and is dependent on large oligomers.<\/jats:p>","DOI":"10.1523\/jneurosci.4736-08.2009","type":"journal-article","created":{"date-parts":[[2009,7,22]],"date-time":"2009-07-22T17:28:53Z","timestamp":1248283733000},"page":"9321-9329","source":"Crossref","is-referenced-by-count":189,"title":["Decreased Brain-Derived Neurotrophic Factor Depends on Amyloid Aggregation State in Transgenic Mouse Models of Alzheimer's Disease"],"prefix":"10.1523","volume":"29","author":[{"given":"Shiyong","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego J.","family":"Garzon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Marchese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Ginsberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly M.","family":"Francis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard T. 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