We studied the growth-associated
protein,
GAP-43 (also called
neuromodulin and B-50) in post-mortem brain tissue using immunohistochemistry and quantitative Western blotting, from patients with
Alzheimer's disease (AD) and age-matched control subjects. By immunohistochemistry, we found a clear reduction of
GAP-43 in the frontal cortex, while in the hippocampus, there was a marked reduction in some areas (dentate molecular layer, stratum moleculare and radiale of CA1 and CA4), while not in other areas (stratum lacunosum, pyramidale and oriens of CA1). Moreover, in the hippocampus, neuritic staining was prominent, and was often associated with
senile plaques. Quantitative analysis showed that
GAP-43 was significantly reduced in AD, both in the frontal cortex (70% of the control value, p < 0.01) and in the hippocampus (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 synaptic vesicle-specific
protein rab3a (r = 0.62; p < 0.05), while no such correlation were found in the hippocampus. In contrast, a significant positive correlation was found between
GAP-43 and the number of
senile plaques in the hippocampus (r = 0.64; p < 0.05), but not in the frontal cortex.
GAP-43 is known to be involved in maintenance of synapses and in neuritic regeneration. Our findings may suggest that in the frontal cortex,
GAP-43 levels decline as a consequence of the synaptic degeneration, while in the hippocampus, sprouting processes, involving
GAP-43, are active.