Tau protein immunoreactivity in dementia of the Alzheimer type. I. Morphology, evolution, distribution, and pathogenetic implications.

The author has used two monoclonal antibodies against tau, Tau-1 and Tau-2, to study at the light microscopic level the morphology, evolution, and distribution of tau immunoreactivity in 21 cases with dementia of the Alzheimer type (DAT) with clinical histories of dementia ranging from 6 months to 10-15 years. They included four cases with Alzheimer's disease (AD), 14 cases with senile dementia of the Alzheimer type (SDAT), and three demented patients with Down's Syndrome (DS). The morphology and distribution of tau immunoreactivity was similar in all three forms of DAT, but the rapidity of evolution, as judged by the duration of dementia and the amount of immunoreactivity, was most severe in DS with dementia and least severe in SDAT. Excessive tau immunoreactivity, as compared with controls which were negative, was present in both astrocytes and vulnerable neurons. Tau-2-positive astrocytes were present throughout the brain and even in regions with no neuronal vulnerability. In evolving cases, several regions that in full-blown cases showed neuronal involvement contained only labeled astrocytes. The neurofibrillary tangles in neuronal involvement contained only labeled astrocytes. The neurofibrillary tangles in neuronal perikarya, the neurites in senile plaques, and an abundance of abnormal neurites found diffusely in the neuropil were intensely stained. In addition, stained granules (ribosomes) were present in both astrocytes and vulnerable neurons. The senile plaques frequently developed around and, on serial sectioning, were almost constantly associated with blood vessels. The amyloid core in senile plaques and the congophilic vessels were unstained. In cases with the shortest duration of dementia, tau immunoreactivity in neurons was found only in the amygdala, the subiculum, the Sommer's sector, the nucleus raphe dorsalis, locus ceruleus, and nucleus basalis of Meynert. In evolving cases, the depths of sulci were more severely affected than the crests of gyri, and the temporoparietal association cortex was more severely involved than the frontal cortex, but, in advanced cases, the depths of sulci, the crests of gyri, and the entire association cortex were equally affected.(ABSTRACT TRUNCATED AT 400 WORDS)