Interaction between APP overexpression and chronic cerebral hypoperfusion.

<p>Barnes maze test showed that APP<i>_Sw/Ind</i>-Tg/BCAS mice exhibited prolonged latency to reach the desired target (A), increased number of errors (B), and increased distance before reaching the desired target (C) compared to the other groups.</p

Chronic cerebral hypoperfusion reduced the Aβ1-42 stained area in the APP<i>_Sw/Ind</i>-Tg mice.

<p>Immunohistochemistry for Aβ1-42 showed intense staining in the hippocampus (A, B, E, F) and in the cerebral cortex (C, D) of the APP<i>_Sw/Ind</i>-Tg/sham mice (n = 4; A, C, E, G) and APP<i>_Sw/Ind</i>-Tg/BCAS mice (n = 6; B, D, F, H). (I) The area positive for Aβ1-42 was analysed in the cortex and the hippocampus. Scale bars: 400 µm (A, B), 300 µm (C–F), 80 µm (G, H).</p

Neuronal density in the cerebral cortex and the hippocampal CA1 and CA3 areas.

<p>(A) The schematic illustration of the regions of interest depicted in the cerebral cortex (size, 0.05×0.5 mm) and the hippocampal CA1 and CA3 areas (0.05×0.25 mm each) of the coronal section of the brain. (B) The density of Nissl-stained neurons was lowest in APP<i>_Sw/Ind</i>-Tg/BCAS mice.</p

Chronic cerebral hypoperfusion affected the number of silver-stained cored plaques in the APP<i>_Sw/Ind</i>-Tg mice.

<p>Modified Bielschowsky staining showed cored plaques in the hippocampus (A, B, G, H) and the cerebral cortex (C, D), and diffuse plaques in the hippocampus (E, F) of the APP<i>_Sw/Ind</i>-Tg/sham mice (n = 6; A, C, E, G) and APP<i>_Sw/Ind</i>-Tg/BCAS mice (n = 4; B, D, F, H). Number of cored plaques was counted in the cortex and the hippocampus (I). Scale bars: 400 µm (A, B), 300 µm (C-F), 80 µm (G, H).</p

Chronic cerebral hypoperfusion increased filter-trap Aβ in the extracellular-enriched, soluble brain fraction.

<p>(A) Filter-trap, Aβ-immunoreactive spot density was increased in samples from BCAS-treated mice, compared to sham-operated littermates. (B) Spot density was significantly increased in BCAS-treated mice (paired t-test; p = 0.0231, n = 4).</p

Significant inverse correlations of the cognitive performances with the neuronal densities.

<p>r = correlation coefficient.</p