Impairment of cathepsin B immunoreactivity in the hippocampal nerve cells with aging in the elderly: Possible evidence for dysfunction of lysosomal proteolysis in relation to the pathogenesis of Alzheimer's disease

Immunohistochemical localization of cathepsin B (CB) in the hippocampal nerve cells was examined in patients ranging from age 18 days to 82 years to examine the change of proteolytic activity of nerve cells with aging through the CB immunoreactivity. Although it varied from case to case, region to region, and to some degree cell to cell, generally, CB immunoreactivity in the nerve cells was weak in the newborn, strong from age 7 to about 60, and decreased in most nerve cells, or the number of nerve cells with impaired CB immunoreactivity increased, after about 60 years of age. This suggests impairment of protein metabolism and/or dysfunction of lysosomal proteolysis in the nerve cells with aging. The last finding may be important as a background or preceding phenomenon that may cause abnormal protein metabolism relating to the formation of neurofibrillary tangles and/or senile plaques with aging and in Alzheimer's disease (AD). The involvement of CB in the metabolism of Aβ-amyloid protein precursors (APP) and the possible close relation of presenilins to APP should also be considered.