Fig. 7.

Zfra is upregulated in the AD hippocampi and interacts with tau and Aβ and blocks NF-κB promoter activation. (A and B) By antibody FRET microscopy, Zfra bound Aβ with a high affinity (FRETc greater than 45) in the hippocampal sections of postmortem AD patients (see yellow punctates in B). However, Zfra may colocalize with Aβ but without binding (FRETc less than 5). (C) Confocal microscopy analysis revealed the colocalization of Zfra with Aβ. (D) Zfra binds PHF-tau with a similar pattern. (E) A bar graph of Zfra binding with Aβ or PHF-tau is shown (n = 20). (F) By filter retardation assay using insoluble human hippocampal extracts, aggregation of Zfra and pSer8-Zfra was increased by 45 and 85%, respectively, in the older AD patients (81 ± 9.7 years old; n = 70), compared to younger nondemented controls (60 ± 13.3 years old; n = 46). Aβ was increased by 170% in the AD patients. (G) Zfra significantly blocked TNF-α (50 ng/mL)-mediated activation of NF-κB promoter in COS7 cells. Abbreviations: AD, Alzheimer's disease; Neg, negative control; PHF, paired helical filament; Pos, positive control; Zfra, zinc finger-like protein that regulates apoptosis.