Expression of truncated presenilin 2 splice variant in Alzheimer's disease, bipolar disorder, and schizophrenia brain cortex.
We have analysed the expression of a truncated variant presenilin 2 protein (PS2V) in frontal cortex from subjects with Alzheimer's disease (AD) and age-matched controls, and compared these results with cortex from bipolar disorder (BP), schizophrenia (SZ) and controls in a second brain bank collection. PS2V protein was detected as a 14 kDa species with antibodies directed to the PS2 N-terminal region and to the new C-terminus created by alternative transcription. PS2V protein levels were significantly increased by two-fold in AD cortex, as compared to age-matched controls. In tissue from the second collection, levels of PS2V were markedly elevated in some BP and SZ cases, but there was no overall difference between diagnostic groups. Our findings support previous evidence for increased expression of this variant PS2 isoform in sporadic AD and suggest this isoform may contribute to neurodegeneration.
Department of Pathology, The University of Melbourne, and The Mental Health Research Institute of Victoria, Grattan St., Parkville, Victoria 3010, Australia.
Margaret J
MJ
Smith
Robyn A
RA
Sharples
Geneviève
G
Evin
Catriona A
CA
McLean
Brian
B
Dean
Geoff
G
Pavey
Emmanuelle
E
Fantino
Richard G H
RG
Cotton
Kazunori
K
Imaizumi
Colin L
CL
Masters
Roberto
R
Cappai
Janetta G
JG
Culvenor
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000378:metabolism*; D003001:Cloning, Molecular / Q000379:methods; D004314:Down Syndrome / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009447:Neuroblastoma; D011180:Postmortem Changes; D053766:Presenilin-2; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*
D008565:Membrane Proteins; C508861:PSEN2 protein, human; D053766:Presenilin-2; D012333:RNA, Messenger