IDENTIFICATION AND NEURON-SPECIFIC EXPRESSION OF THE S182 PRESENILIN-I PROTEIN IN HUMAN AND RODENT BRAINS/

Many individuals with familial Alzheimer disease (FAD) have mutations in a gene termed S182 or presenilin I (PS-I), Currently, the PS-I gene product has not been identified and its function remains unknown, Her e we report that affinity purified antibodies against the predicted am ino acid sequence of the PS-I gene product detected in homogenates of human, mouse, and rat brains a single antigen of approximately 48 kDa. This antigen was also present in immortalized human and mouse neurona l cell cultures, Brain tissue fractionation showed that all PS-I antig en was found in the membrane fraction, In stained tissue sections of m ouse central nervous system (CNS), PS-I antigen was found only in neur ons throughout brain and spinal cord and was located within cell bodie s, axons, and dendrites, Remarkably the relative partition among these three compartments varied dramatically, A striking feature of PS-I ex pression was its intense concentration in some (but not all) dendrites , at levels substantially above those in the parent perikarya, In most of the cerebrum, PS-I staining in axons was very weak or undetectable , By contrast, many axons in portions of the brainstem and in the spin al cord showed marked PS-I immuno-reactivity, Similarly, staining of s ections from human temporal cortex showed that PS-I was present mainly in neuronal cell bodies and dendrites, These data show that in the CN S, PS-I is expressed mainly in neurons and suggests that this protein may perform a neuron specific function, The pattern of PS-I expression in the CNS would suggest that the premature neurodegeneration associa ted with PS-I mutations involves a primary neuronal process rather tha n a secondary effect of PS-I produced in non-neuronal cells. (C) 1996 Wiley-Liss, Inc.