The extracellular matrix in Alzheimer's disease
The perineuronal net (PN) is a specialised region of extracellular matrix around some neurons, particularly GABAergic neurons that contain the calcium binding protein, parvalbumin (PV). The negatively charged glycosaminoglycan side chains of chondroitin sulphate proteoglycans, a major constituent of the PN, create a polyanionic environment around neurons that is thought to be important in the buffering of ions. Maintaining ion homeostasis around the inhibitory PV-positive neurons is critical in order to sustain their fast-firing rates. Loss or disruption of inhibitory input, particularly to glutamatergic cells could result in excitotoxicity and cell death. The PN is also important in the development, stabilisation and remodelling of synapses, in maintaining the trophic microenvironment around neurons and in synaptic plasticity. Neurodegeneration, the considerable loss of synapses and the inflammatory reaction that occurs in Alzheimer's disease (AD) is likely to affect the PN. Glial cells, activated as part of the inflammatory response to the deposition of Î²-amyloid (AÎ²) and formation of neurofibrillary tangles, release matrix metalloproteinases (MMPs) that are capable of degrading the PN. This thesis describes studies of PN N-acetylgalactosamine and PV-positive neurons in AD, and their relationship to parenchymal tau, AÎ², microglia, astrocytes, and MMPs-2, -3 and -9. The outcome of these studies showed that the PV-positive neurons tend to be spared in AD but there is degradation of surrounding PNs.