Most cases of dementia with hippocampal sclerosis may represent frontotemporal dementia.

Hippocampal sclerosis dementia (HSD) is a disease of unknown etiology and pathogenesis. To determine whether HSD cases could be reclassified as variants of frontotemporal dementia (FTD), a heterogeneous group of disorders, 18 brain autopsy cases previously diagnosed as HSD were re-evaluated. In 11 cases, ubiquitinated neuronal inclusions, similar to those of motor neuron disease inclusion dementia (MNDID), were found. Brain levels of soluble and insoluble tau were normal. Most patients with pathologic findings of HSD may actually have the MNDID variant of FTD.

RNA editing of the glutamate receptor subunits GluR2 and GluR6 in human brain tissue.

Editing of mRNA in the coding region of the second transmembrane domain of glutamate receptor subunits GluR2, GluR5, and GluR6 involves a change of the base A in genomic DNA to the base G in mRNA as described in rat brain. To determine whether this reaction occurs in humans as well as rats, we studied RNA editing of GluR2 and GluR6 in human brain. We compared the extent of editing in controls and cases with Huntington's disease. To assay the extent of editing in brain RNA, first strand cDNA was amplified using the polymerase chain reaction yielding a product across the region of the second transmembrane spanning segment in which editing takes place in rats. The PCR product was incubated with the restriction enzyme BbvI, which recognizes the sequence GCAGC present in the nonedited sequence of the mRNA in subunits GluR2 and GluR6. Thus, BbvI cuts the nonedited version but leaves the edited version intact. As in the rat, the GluR2 subunit mRNA was completely edited in human brain. The GluR6 subunit was nearly completely edited in all gray matter structures investigated including cortex, striatum, thalamus, hippocampus, amygdala, and cerebellum with extent of editing ranging from 89% in the cerebellum to 95% in the cortex and striatum. No significant differences in the extent of RNA editing were apparent in control versus Huntington's disease brains. To compare the extent of editing in neurons and glia in the brain, editing in cerebral cortex (predominantly gray matter and thus neurons) was compared with editing in corpus callosum (white matter and thus nearly completely glial cells).(ABSTRACT TRUNCATED AT 250 WORDS)

Reductions in acidic amino acids and N-acetylaspartylglutamate in amyotrophic lateral sclerosis CNS.

Acidic excitatory amino acids have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). We now report that, in addition to selective regional reductions in endogenous aspartate and glutamate, N-acetylaspartate (NAA), and N-acetylaspartylglutamate (NAAG) are also decreased in the CNS, whereas the activity of N-acetylated-alpha-linked-amino dipeptidase (NAALADase) is increased. In cervical cord, the concentrations of aspartate and glutamate were decreased significantly in the ventral horn; NAA was decreased in the ventral horn, dorsal horn and ventral column, whereas NAAG was decreased in all regions of the cord examined, except the posterior column. NAALADase activity was increased in the ventral column. In motor cortex of ALS patients, aspartate and glutamate were decreased and NAALADase activity was increased in both gray and white matter; whereas NAAG was decreased in gray matter alone. None of these parameters was affected in the cerebral cortex of the Huntington's patients. Of the markers examined, the alterations in the levels of NAAG most closely parallel the cellular neuropathology in ALS.