Growth-associated protein GAP-43 in the frontal cortex and in the hippocampus in Alzheimer's disease: an immunohistochemical and quantitative study

We studied the growth-associated protein, GAP-43 (also called neuromodulin and B-50) in post-mortem brain tissue using immunohistochemistry and quanti tative Western blotting, from patients with Alzheimer's disease (AD) and ag e-matched control subjects. By immunohistochemistry, we found a clear reduc tion of GAP-43 in the frontal cortex, while in the hippocampus, there was a marked reduction in some areas (dentate molecular layer, stratum molecular e and radiale of CA1 and CA4), while not in other areas (stratum lacunosum, pyramidale and oriens of CA1). Moreover, in the hippocampus, neuritic stai ning was prominent, and was often associated with senile plaques. Quantitat ive analysis showed that GAP-43 was significantly reduced in AD, both in th e frontal cortex (70% of the control value, p < 0.01) and in the hippocampu s (81% of the control value, p < 0.05). In the frontal cortex, there was a significant negative correlation between GAP-43 and duration of dementia (r = -0.58; p < 0.02) and a positive correlation between GAP-43 and the synap tic vesicle-specific protein rab3a (r = 0.62; p < 0.05), while no such corr elation were found in the hippocampus. In contrast, a significant positive correlation was found between GAP-43 and the number of senile plaques in th e hippocampus (r = 0.64; p < 0.05), but not in the frontal cortex. GAP-43 i s known to be involved In maintenance of synapses and in neuritic regenerat ion. Our findings may suggest that in the frontal cortex, GAP-43 levels dec line as a consequence of the synaptic degeneration, while in the hippocampu s, sprouting processes, involving GAP-43, are active.