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Identification and neuron specific expression of the S182/presenilin I protein in human and rodent brains
Author(s) -
Elder G.A.,
Tezapsidis N.,
Carter J.,
Shioi J.,
Bouras C.,
Li H.C.,
Johnston J.M.,
Efthimiopoulos S.,
Friedrich V.L.,
Robakis N.K.
Publication year - 1996
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19960801)45:3<308::aid-jnr13>3.0.co;2-#
Subject(s) - biology , spinal cord , neuron , central nervous system , cerebrum , antigen , human brain , microbiology and biotechnology , brainstem , neuroscience , immunology
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. Here we report that affinity purified antibodies against the predicted amino 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 neuronal cell cultures. Brain tissue fractionation showed that all PS‐I antigen was found in the membrane fraction. In stained tissue sections of mouse central nervous system (CNS), PS‐I antigen was found only in neurons throughout brain and spinal cord and was located within cell bodies, axons, and dendrites. Remarkably the relative partition among these three compartments varied dramatically. A striking feature of PS‐I expression 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 spinal cord showed marked PS‐I immunoreactivity. Similarly, staining of sections from human temporal cortex showed that PS‐I was present mainly in neuronal cell bodies and dendrites. These data show that in the CNS, 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 associated with PS‐I mutations involves a primary neuronal process rather than a secondary effect of PS‐I produced in non‐neuronal cells. © 1996 Wiley‐Liss, Inc.