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.
Smith
Margaret J
MJ
Department of Pathology, The University of Melbourne, and The Mental Health Research Institute of Victoria, Grattan St., Parkville, Victoria 3010, Australia.
Sharples
Robyn A
RA
Evin
Geneviève
G
McLean
Catriona A
CA
Dean
Brian
B
Pavey
Geoff
G
Fantino
Emmanuelle
E
Cotton
Richard G H
RG
Imaizumi
Kazunori
K
Masters
Colin L
CL
Cappai
Roberto
R
Culvenor
Janetta G
JG
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