Embryonic genes expressed in Alzheimer's disease brains.

Alzheimer's disease (AD)-specific or characteristic gene expression was explored by the identification of cDNA clones by means of differential screening for embryonic brain cDNA library with 32P-labeled cDNA probes prepared from mRNA of AD and normal human brains. To isolate neuronal genes in degenerating neurons, we used rat embryonic cDNA library at stage day 15 when glial cells developed poorly in the brain. Seventeen embryonic genes were identified as embryonic alpha-tubulin, embryonic beta-tubulin, hnRNP, protein L-isoaspartyl methyltransferase (PIMT), ferritin heavy chain, type IV collagen, actin-binding protein cofilin, profilin and nine novel sequences designated as A1-9. We characterized these genes by Northern blot analysis, RNase protection assay and immunohistochemical studies, showing that PIMT and a novel gene designated as A5 showed the transcriptional up-regulation in AD brains. In addition, the immunohistochemical studies showed PIMT, type IV collagen, and cofilin were associated with neurofibrillary tangles in degenerating neurons, brain vessels in affected regions, and synaptosomal structures in AD brains, respectively. The catalogue presented here also showed the involvement of cytoskeletal proteins, cytoskeleton-associated proteins, and an iron-storage protein, suggesting the presence of regenerating activity and the abnormal metabolisms in affected neurons of AD brains.