Cortical areas abundant in extracellular matrix chondroitin sulphate proteoglycans are less affected by cytoskeletal changes in Alzheimer's disease

In the human brain, the distribution of perineuronal nets occurring as latt ice-like neuronal coatings of extracellular matrix proteoglycans ensheathin g several types of non-pyramidal neurons and subpopulations of pyramidal ce lls in the cerebral cortex is largely unknown. Since proteoglycans are pres umably involved in the pathogenesis of Alzheimer's disease, we analysed the distribution pattern of extracellular chondroitin sulphate proteoglycans i n cortical areas, including primary motor, primary auditory and several pre frontal and temporal association areas, in normal human brains and in those showing neuropathological criteria of Alzheimer's disease. In both groups, neurons with perineuronal nets were most numerous in the primary motor cor tex (approximately 10% in Brodmann's area 4) and in the primary auditory co rtex as a representative of the primary sensory areas. Their number was low er in secondary and higher order association areas. Net-associated pyramida l cells occurred predominantly in layers III and V in motor areas, as well as throughout lower parts of layer III in the primary auditory cortex and n eocortical association areas. In the entorhinal cortex, net-associated pyra midal cells were extremely rare. In brains showing hallmarks of Alzheimer's disease, the characteristic patterns of hyperphosphorylated tau protein, s tained with the AT8 antibody, largely excluded the zones abundant in perine uronal nets and neuropil-associated chondroitin sulphate proteoglycans. As shown in double-stained sections, pyramidal and non-pyramidal neurons enshe athed by perineuronal nets were virtually unaffected by the formation of ne urofibrillary tangles even in severely damaged regions. The distribution pa tterns of amyloid a deposits overlapped but showed no congruence with that of the extracellular chondroitin sulphate proteoglycans. It can be concluded that low susceptibility of neurons and cortical areas t o neurofibrillary changes corresponds with high proportions of aggregating chondroitin sulphate proteoglycans in the neuronal microenvironment. (C) 19 99 IBRO. Published by Elsevier Science Ltd.