Presenilin-1, amyloid precursor protein and amyloid precursor-like protein 2 mRNA levels in human superior frontal cortex during aging.
The presenilin-1 (PS-1) and amyloid precursor protein (APP) genes carry mutations which co-segregate with early-onset familial Alzheimer's disease. The APP and PS-1 gene products may be involved in the aetiology of the more common late onset form of Alzheimer's disease, where increasing age is a major risk factor. To investigate whether age affected mRNA expression of these genes, we quantified PS-1, total APP, APP containing the kunitz-type protease inhibitor (KPI) domain and amyloid precursor-like protein 2 (APLP2) mRNAs in post-mortem superior frontal cortices from 23 control subjects aged 38 to 89 years using solution hybridisation-RNase protection assays. PS-1, total APP, APP KPI and APLP2 mRNA levels were unchanged over this age range. PS-1 was the least abundant mRNA, at approximately 7% of total APP, the most highly expressed mRNA studied (10.8 copies/pg total RNA). The proportion of total APP encoding the KPI domain (approximately 52%) was unaffected by age. APLP2 mRNA was present at approximately 29% of the total APP mRNA level. Significant positive correlations were present between total APP, APP KPI and APLP2 mRNA levels. These results indicate that the increased prevalence of Alzheimer's disease cannot be attributed to alterations in cortical PS-1, APP and APLP2 mRNA levels or APP KPI splicing during aging.
Flood
F M
FM
Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Novum KFC, Huddinge, Sweden. fiona.flood@kfcmail.hs.sll.se
Cowburn
R F
RF
Johnston
J A
JA
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010455:Peptides; D010940:Plant Proteins; D053764:Presenilin-1; D012333:RNA, Messenger / Q000032:analysis; D014361:Trypsin Inhibitors / Q000378:metabolism
C489697:APLP1 protein, human; C084104:APLP2 protein, human; D016564:Amyloid beta-Protein Precursor; C053865:Kunitz-type protease inhibitor, plant; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; D010455:Peptides; D010940:Plant Proteins; D053764:Presenilin-1; D012333:RNA, Messenger; D014361:Trypsin Inhibitors