APP WITH KUNITZ-TYPE PROTEASE INHIBITOR DOMAIN (KPI) CORRELATES WITH NEURITIC PLAQUE DENSITY BUT NOT WITH CORTICAL SYNAPTOPHYSIN IMMUNOREACTIVITY IN ALZHEIMERS-DISEASE AND NONDEMENTED AGED SUBJECTS - A MULTIFACTORIAL ANALYSIS

The formation of betaA4 amyloid protein in neuritic plaques in Alzheim er's disease (AD) and advanced age is a complex process that involves a number of both cellular and molecular mechanisms, the interrelations of which are not yet completely understood. We have examined quantita tively, in AD and aged controls an extended spectrum of amyloid plaque -related cellular and molecular factors and the cortical synaptophysin immunoreactivity (synaptic density) in order to check for interrelati ons between them by multifactorial analysis. In 3 cases of senile deme ntia of the Alzheimer type (SDAT) aged 72, 80 and 82 years, and 9 cont rols aged 43-88 (mean age 65) years, the cortical synaptophysin immuno reactivity was assessed, together with the numbers of neurons, astrocy tes and microglial cells, senile plaques, of tangle-bearing neurons, a nd the amount of betaA4 amyloid precursor protein (APP) with and witho ut the Kunitz type serine protease inhibitor (KPI) domain. The main re sults were: APP including the KPI domain (KPI-APP) correlated with the number of neuritic plaques, regardless of whether they occurred in SD AT or non-demented controls. There was no significant difference in th e amount of KPI-APP between SDAT and controls. Conversely, APP695 (wit hout KPI) was significantly reduced in SDAT. KPI-APP did not correlate with the synaptophysin immunoreactivity (RGVA), while APP695 showed a significant correlation with the latter in all evaluations. It also c orrelated with the neuron counts, which was not true for KPI-APP. Thes e results support previous findings indicating that KPI-APP is an impo rtant local factor for amyloid deposition in the neuritic plaques, bot h in AD and in non-demented aged people. On the contrary, KPI-APP does not seem to be significantly involved in the mechanisms of synaptic c hange outside of the plaques.