FE65 in Alzheimer's disease - Neuronal distribution and association with neurofibrillary tangles

FE65, a protein expressed in the nervous system, has the ability to bind th e C-terminal domain of the amyloid precursor protein. This suggests a role for FE65 in the pathogenesis of Alzheimer's disease (AD), The present study mas conducted to find out if the distribution of FE65 immunoreactivity was affected during the course of AD, and to determine the degree of co-locali zation of FE65 with other proteins known to be involved in AD. Single immun operoxidase-labeling experiments, conducted on six sporadic AD patients and six nondemented age-matched controls, showed that the proportion of volume occupied by FE65 immunoreactivity was not modified in the isocortex of AD patients. However, in hippocampal area CA4, increased FE65 immunoreactivity seemed to be associated with the severity of the disease. Double-immunoflu orescent labeling did not show any clear co-localization of FE65 with the a myloid precursor protein. FE65 immunoreactivity was also absent from focal and diffuse deposits of the P-amyloid peptide. Unexpectedly double labeling experiments showed a co-localization of FE65 and tau proteins in intracell ular tangles. Ultrastructural observations confirmed that FE65 was associat ed with paired helical filaments.