Differential synaptic loss in the cortex in Alzheimer's disease: a study using archival material.

We have developed techniques to utilize immunocytochemical localization of synaptic protein (SNAP-25) in conjunction with image analysis to investigate synaptic loss in readily available archival material. Sections from 5 cortical regions were examined in cases of Alzheimer's disease (n = 7) and controls (n = 5). Image analysis was used to determine a relative synaptic index (RSI) and probe for changes in synaptic integrity. RSI value for cortical regions did not differ in controls. RSIs from sulci and gyri were significantly correlated in Brodmann areas 6, 9 and 18 (40 and 52 approached significance). Cases with Alzheimer's disease showed decreases in sulcal and gyral RSI values of between 60% (Brodmann area 6 < 0.01) and 10% (Brodmann area 18 > 0.4) and a lack of correlation in sulco-gyral values except in Brodmann area 18. We have demonstrated that synaptic pathology is heterogeneous with frontal cortex most and occipital cortex least affected. Sulci and gyri are affected to different degrees. The underlying cytoarchitecture of the cortex and its pattern of connectivity appears to have a considerable influence on the degree and extent of synaptic pathology.