Diversity of high-molecular-weight tau proteins in different regions of the nervous system.

We show in this work that high-molecular-weight (HMW) tau transcripts are present in all the regions of the CNS and PNS studied, i.e., the dorsal root ganglia (DRG), spinal cord, cerebellum, and forebrain. However, the relative amount of HMW and low-molecular-weight (LMW) tau variants and their sequence vary depending on the region. Two HMW tau variants that contain either both exons 4A and 6 or only exon 6 have been identified in the adult spinal cord by PCR amplification and sequenced. In contrast, a single HMW tau variant that contains exon 4A but not exon 6 was detected in the adult rat DRG. This means that at least part of the HMW tau expressed in the spinal cord is produced locally and not transported within this structure by fibers arising in the DRG. The expression of the HMW tau isoforms is developmentally regulated both quantitatively and qualitatively in the spinal cord. At immature stages very low levels of the HMW tau transcript containing both exons 4A and 6 are expressed, whereas the tau species containing only exon 6 is absent. Rat forebrain, rat cerebellum, and human forebrain express much lower levels of HMW tau transcripts compared with the spinal cord and the DRG. Their sequence contains both exons 4A and 6, i.e., is identical to that of the major HMW tau transcript detected in the adult rat spinal cord. The minor spinal cord species that contains only exon 6 was not identified in the rat forebrain and rat cerebellum but was present among the human brain PCR fragments.(ABSTRACT TRUNCATED AT 250 WORDS)