A Thr<sup>668</sup>Ala mutation on APP prevents the short-term memory deficit of FDD<sub>KI</sub> mice.

<p>(<b>a</b> and <b>b</b>) In RAWM testing, FDD<sub>KI</sub>/<i>APP<sup>TA/TA</sup></i>, FDD<sub>KI</sub>/<i>APP<sup>TA/WT</sup></i>, <i>APP<sup>TA/TA</sup></i>, <i>APP<sup>TA/WT</sup></i> mice made the same number of errors as WT mice at both 5.5 months and 9 months of age. At 5.5 months of age, FDD<sub>KI</sub> mice made significantly more errors at A4 (versus FDD<sub>KI</sub>/APP<sup>TA/TA </sup><i>P</i> = 0.0007; versus FDD<sub>KI</sub>/APP<sup>TA/WT</sup> P = 0.0028; versus WT <i>P = </i>0.0005) and R (versus FDD<sub>KI</sub>/APP<sup>TA/TA </sup><i>P</i> = 0.0017; versus FDD<sub>KI</sub>/APP<sup>TA/WT</sup> P = 0.0005; versus WT <i>P</i> = 0.0005) (<b>a</b>). Similar results are found at 9 months of age; FDD<sub>KI</sub> mice made significantly more errors at A4 (versus FDD<sub>KI</sub>/APP<sup>TA/TA </sup><i>P</i> = 0.0004; versus FDD<sub>KI</sub>/APP<sup>TA/WT</sup> P = 0.019; versus WT <i>P</i> = 0.0003) and R (versus FDD<sub>KI</sub>/APP<sup>TA/TA </sup><i>P</i> = 0.0006; versus FDD<sub>KI</sub>/APP<sup>TA/WT</sup> P = 0.004; versus WT <i>P</i><0.0001). Thus, the APP<sup>TA/TA</sup> and APP<sup>TA/WT</sup> point mutations prevent the development of working memory deficits in FDD<sub>KI</sub> mice (<b>b</b>). (<b>c</b> and <b>d</b>) WT, FDD<sub>KI</sub>, FDD<sub>KI</sub>/<i>APP<sup>TA/TA</sup></i>, FDD<sub>KI</sub>/<i>APP<sup>TA/WT</sup></i>, <i>APP<sup>TA/TA</sup></i> and <i>APP<sup>TA/WT</sup></i> mice have similar speed (c) and need similar time (d) to reach a visible platform.</p>