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. 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.
Elder
G A
GA
Department of Psychiatry, Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029-6547, USA.
Tezapsidis
N
N
Carter
J
J
Shioi
J
J
Bouras
C
C
Li
H C
HC
Johnston
J M
JM
Efthimiopoulos
S
S
Friedrich
V L
VL
Robakis
N K
NK
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology; D001923:Brain Chemistry / Q000502:physiology*; D002460:Cell Line; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D009410:Nerve Degeneration / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D053764:Presenilin-1; D051381:Rats
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1