Figure 8

Toxicity of wild type and variant Aβ in adenovirus transfection model. Cultured rat cortical neurons were transfected with adenovirus engineered for doxycycline-inducible expression of wild type or variant Aβ, and toxicity was assayed by scoring of apoptotic nuclei or synaptophysin expression. A. Relative toxicity (pyknotic nuclei fraction) in neurons transfected with Aβ-expressing adenovirus with (+ Dox) and without induction. Transfection with adenovirus expressing Aβ wild type or Aβ L17P leads to significant toxicity after transgene induction (* P < 0.001), while transfection with adenovirus expressing Aβ G37L, or co-transfection with Aβ wild type and Aβ G37L, does not lead to significant toxicity after doxycycline induction. B. Representative processes containing synapses labeled with synaptophysin in Aβ wild type and Aβ G37L expressing neuronal cultures. Control panel refers to non-induced cultures. Scale bar, 5 μm. C. Analysis of puncta density (number of synapses per 25 μm of neurite) indicated fewer synapses in Aβ wild type expressing cells compared to non-induced controls. Intraneuronal Aβ G37L and co-expression of Aβ wild type and Aβ G37L resulted in no significant synapse alterations. Data from 3-5 different cultures from 3 independent isolations. n (neurites) = 154 Aβ wild type, 98 Aβ G37L, 118 Aβ wild type + G37L. (* = P < 0.001, NS = not significant, P > 0.1). Error bars represent SEM.