Quantification of axonal loss in Alzheimer’s disease: an image analysis study

The density of axons in the optic nerve, olfactory tract and corpus callosum was quantified in non-demented elderly subjects and in Alzheimer’s disease (AD) using an image analysis system. In each fibre tract, there was significant reduction in the density of axons in AD compared with non-demented subjects, the greatest reductions being observed in the olfactory tract and corpus callosum. Axonal loss in the optic nerve and olfactory tract was mainly of axons with smaller myelinated cross-sectional areas. In the corpus callosum, a reduction in the number of ‘thin’ and ‘thick’ fibres was observed in AD, but there was a proportionally greater loss of the ‘thick’ fibres. The data suggest significant degeneration of white matter fibre tracts in AD involving the smaller axons in the two sensory nerves and both large and small axons in the corpus callosum. Loss of axons in AD could reflect an associated white matter disorder and/or be secondary to neuronal degeneration.