TUNEL and growth factor expression in the prefrontal cortex of Alzheimer patients over 80 years old.

To elucidate factors underlying the increased risk of developing Alzheimers disease (AD) in older individuals, the prefrontal cortices of younger (58-79 years) and of older (over 80 years) AD patients were examined by silver impregnation, TUNEL assay and immunohistochemistry for hyperphosphorylated tau, LDH and two growth factors (BDNF, NGF). Quantitative data were compared with those of age-matched controls. TUNEL-positive cells were mainly located in superficial cortical layers of younger and in deeper layers of older AD patients. Their density was more than 5 times higher in older AD than in younger AD (p < or = 0.05), but apoptotic cell morphology was rarely seen. Significantly more neuronal somas were contacted by degenerating fibers both in younger and older AD cortices. Density of tau-immunoreactive cells, which were virtually absent in controls, was twice as high in older AD patients as in younger AD individuals (p < or = 0.05). In younger AD, TUNEL positive cells generally lacked tau immunoreaction, whereas in older AD, most cells were double-labeled for hyperphosphorylated tau and TUNEL (p < or = 0.05). Numerical density of BDNF-immunoreactive cells was significantly reduced by 20 percent in older AD patients, compared to both control individuals and younger AD patients, whereas density of NGF-positive cells was the same in all patient groups examined. The distinct differences between younger and older AD patients suggest a faster progression of AD in older patients.