Oligodendrocytes are specialised glial cells that myelinate CNS axons. Myelinated axons are bundled together
into white matter tracts that interconnect grey matter areas of the brain and are essential for rapid, integrated neuronal
communication and cognitive function. Life-long generation of oligodendrocytes is required for myelination of new neuronal
connections and repair of myelin lost through natural ‘wear and tear’. This is the function of a substantial population
of adult oligodendrocyte progenitors (OPs). Notably, there is white matter shrinkage and decreased myelination in the
ageing brain, which is accelerated in dementia. The underlying causes of myelin loss in dementia are unresolved, but it
implies a decline in the regenerative capacity of OPs. A feature of OPs is that they form neuron-glial synapses and respond
to glutamate released by neurons via a range of glutamate receptors. Glutamate neurotransmission onto OPs is proposed
to regulate their proliferation and differentiation into myelinating oligodendrocytes. Here, we discuss evidence that
deregulation of glutamate neurotransmission in dementia and compromised generation of oligodendrocytes from OPs are
key features of myelin loss and associated cognitive decline.
Keywords: Alzheimer’s disease, dementia, glutamate. myelin, oligodendrocyte progenitor, oligodendrocyte, white matter.
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