LOSS OF NONPHOSPHORYLATED NEUROFILAMENT IMMUNOREACTIVITY IN TEMPORAL CORTICAL AREAS IN ALZHEIMER'S DISEASE

The distribution of immunoreactive neurons with nonphosphorylated neurofilament protein (SM132) was studied in temporal cortical areas in normal subjects and in patients with Alzheimer's disease (AD). SM132 immunopositive neurons were localized mainly in cortical layers II, III, V and VI, and were medium to large-sized pyramidal neurons. Patients with AD had prominent degeneration of SM132 positive neurons in layers III and V of Brodmann areas 38, 36, 35 and 20; in layers II and IV of the entorhinal cortex (Brodmann area 28); and hippocampal neurons. Neurofibrillary tangles (NFTs) were stained with Thioflavin-S and with an antibody (AT8) against hyperphosphorylated tau. The NFT distribution was compared to that of the neuronal cytoskeletal marker SM132 in these temporal cortical regions. The results showed that the loss of SM132 immunoreactivity in temporal cortical regions of AD brain is paralleled by an increase in NFTs and AT8 immunoreactivity in neurons. The SM132 immunoreactivity was drastically reduced in the cortical layers where tangle-bearing neurons are localized. A strong SM132 immunoreactivity was observed in numerous neurons containing NFTs by double-immunolabeling with SM132 and AT8. However, few neurons were labeled by AT8 and SM132. These results suggest that the development of NFTs in some neurons results from some alteration in SM132 expression, but does not account for all, particularly, early NFT-related changes. Also, there is a clear correlation of NFTs with selective population of pyramidal neurons in the temporal cortical areas and these pyramidal cells are specifically prone to formation of paired helical filaments. Furthermore, these pyramidal neurons might represent a significant portion of the neurons of origin of long corticocortical connection, and consequently contribute to the destruction of memory-related input to the hippocampal formation. Published by Elsevier Ltd on behalf of IBRO.