The production of the Alzheimer amyloid precursor protein (APP) in extraneuronal tissue does not increase in old age.
Alzheimer's disease (AD) is characterized by the cerebral deposition of beta-amyloid (A beta). A beta plaques also occur in the brains of healthy aged individuals, and A beta concentrations are increased in the cerebrospinal fluid (CSF) in old age. Based on results from an in vitro senescence model on human fibroblasts, it was proposed that the production of the beta-amyloid precursor protein (APP) was increased during aging. No information was available as to whether APP production was also augmented in aged humans. It was therefore the aim of the present study to analyze APP in connective tissue, skeletal muscle, peripheral blood mononuclear cells, and serum samples from young and aged healthy individuals. APP production was assessed by Northern and Western blotting. The expression of the different APP isoforms was studied by reverse transcription-polymerase chain reaction (RT-PCR) technique. The results demonstrate that APP messenger ribonucleic acid (mRNA) and protein concentrations were identical in blood and tissue samples from young and aged individuals and that there were no age-dependent changes in the APP isoform production pattern. Thus, our data strongly argue against the possibility of an altered production of APP during healthy aging and underline the point that in vitro aging models may not accurately reflect the in vivo situation.
Niederwolfsgruber
E
E
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.
Schmitt
T L
TL
Blasko
I
I
Trieb
K
K
Steger
M M
MM
Maczek
C
C
Hager
J
J
Bobak
K
K
Steiner
E
E
Grubeck-Loebenstein
B
B
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D003238:Connective Tissue / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008875:Middle Aged; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger