Figure 5

Cortical Aβ peptide deposition induces glutamate-dependent hippocampal Tau phosphorylation. Cortical (Cx) and hippocampal (Hi) neurons were cultured in μFD chambers as in Figure 2a. a, c. Representative fluorescence micrograph ofcortical neurons (left μFD chamber) after immunostaining of phosphorylated Tau (pTau Thr231, red; β-tubulin, green). Effect of Aβ42 oligomers and Aβ25-35 peptides on synaptic connections. Cortical and hippocampal neurons were cultured in μFD chambers as shown in a. b,c) Representative fluorescence micrographs from somato-dendritic compartment of Cx neurons (left panels) and from Hi neurons in the distal chamber receiving cortical fibers (right panels). b, d. Representative fluorescence micrograph of hippocampal neurons receiving cortical axons after immunostaining of pTau (Thr231; pseudo-colors). b) Control conditions (Ø/Ø), d) cortical treatment with Aβ25-35 (10 nM) for 24 h. Scale bar: 20 μM. e. Quantification of pTau-positive hippocampal neurons after 24 h cortical exposure to fibrillar Aβ25-35, oligomeric Aβ42 or fibrillar Aβ42 (10 nM, each) in the presence or absence of the NMDAR antagonist MK801 (10 μM). The results were compared to pTau-positive neurons induced by exposure of Hi neurons to okadaic acid (1 nM, 24 h) (n = 3 **P < 0.01; ***P < 0.001, ANOVA).