Chapter 19 Transcriptional and translational regulatory mechanisms during normal aging of the mammalian brain and in Alzheimer's disease

Molecular cloning of amyloid cDNA derived from mRNA of the Alzheimer disease brain: coding and noncoding regions of the fetal precursor mRNA are expressed in the cortex.

“…The AD brain is rich in ribonucleases (38) and a combination of transcriptional and degradative factors have been implicated in lowering RNA levels (19). However, the presence of partly degraded RNA in some postmortem preparations may be unrelated to the usual metabolic pathway for RNA turnover.…”

“…Two different Agtll recombinant cDNA libraries were prepared separately from A67 and A77 postmortem brain poly(A)+ RNAs by the general methods described (16,19,20). The A67 library described elsewhere (16) was used previously to obtain an insert corresponding to glial fibrillary acidic protein (GFAP) mRNA (15,16,21).…”

Genetic Expression of Amyloid and Glial-specific Protein in the Alzheimer Brain

“…Cytophotometric analyses of biopsied AD cortical tissue revealed that the neuronal RNA content was decreased relative to controls 32 , 33 . However, we observed that poly(A + ) RNA is retained by AD postmortem brains in amounts that are sufficient for protein synthesis and molecular cloning investigations 7–9 , 27 , 30 , 31 …”

“…Early investigations were carried out on human brain tissue by measuring the yields and the stimulation of protein synthesis in vitro to determine the extent to which RNA survived the postmortem interval. Examination of these two parameters appeared germane to the study of an age‐related disease because a host of animal experiments, carried out over the past two decades, had indicated that RNA levels and protein synthesizing capacity progressively decline during aging of the mammalian brain 31 . Postmortem studies from our own laboratory, as well as from others, demonstrated decreased intracellular RNA 34–39 and yield of RNA 30 , 31 , 40–43 .…”

“…Examination of these two parameters appeared germane to the study of an age‐related disease because a host of animal experiments, carried out over the past two decades, had indicated that RNA levels and protein synthesizing capacity progressively decline during aging of the mammalian brain 31 . Postmortem studies from our own laboratory, as well as from others, demonstrated decreased intracellular RNA 34–39 and yield of RNA 30 , 31 , 40–43 . Cytophotometric analyses of biopsied AD cortical tissue revealed that the neuronal RNA content was decreased relative to controls 32 , 33 .…”