Neuronal localization of Presenilin-1 and association with amyloid plaques and neurofibrillary tangles in Alzheimer?s disease

BUSCIGLIO J; H. HATMANN; A. LORENZO; C. WONG; K. BAUMANN; B. SOMMER; M. STAUFENBIEL ; B.A. YANKNER

SOC NEUROSCIENCE

Año: 1997 vol. 17 p. 5101 - 5101

utations in the presenilin-1 (PS1) gene is a cause of early- onset familial Alzheimer´s disease (AD). Endogenous PS1 is associated with the endoplasmic reticulum in the cell body of undifferentiated SH-SY5Y neuroblastoma cells. At early stages of neuronal differentiation in rat hippocampal culture, PS1 appears in all neuritic processes and in growth cones. In mature differentiated neurons, PS1 is concentrated in the somatodendritic compartment but is also present at lower levels in axons. A similar localization of PS1 is observed in vivo in neurons of the adult human cerebral cortex. In sporadic AD, PS1 appears in the dystrophic neurites of mature amyloid plaques and co-localizes with a subset of intraneuronal neurofibrillary tangles (NFTs). About 30% of hippocampal NFTs are labeled with a highly specific antibody to the PS1 C-terminal loop domain but not with an antibody to the PS1 N terminus. This observation is consistent with a potential association of the PS1 C-terminal fragment