The perforant pathway is a pathway of neuron axons which arises from layers II, III, V, and VI of the entorhinal cortex, establishing connections with the dentate gyrus and the Ammon's horn in the hippocampus as it perforates the subiculum. The perforant pathway is also called the perforating fasciculus. Neurons in layer II send their axons to the dentate gyrus and Ammon's horn field 3 (CA3), whereas layer III and layer V nerve cells project to field CA1 of Ammon's horn and the subiculum. Perforant pathway damage results in progresive neurons (nerve cells) death and somal atrophy in layer II of entorhinal cortex and functional impairment with increasing post-damage age.
Perforant pathway and Alzheimer's disease
In order to compare the effects of normal aging and Alzheimer's disease (AD) on the elements of the perforant pathway, scientists from the Aging Research Centre Laboratory compared relative perikaryal numbers, which is determined by counting cell bodies and estimating volumes, in layer II of the entorhinal cortex (ERC) with synaptic quantities, estimated from immunoreactivity for the synaptic terminal protein synapsin I and dentate gyrus volume, in the molecular layer of the dentate gyrus (DG). The brains of 5 young and 9 elderly cognitively normal individuals, and of 9 AD patients were studied. In normal aging we found a significant age-related decline in perikaryal numbers in the ERC without demonstrable synaptic loss in the DG. In AD there was marked and equivalent, (or proportional) reduction in both ERC perikaryal numbers and DG synapses. These data suggest that in normal aging remaining neurons may continue to support a full array of synapses, perhaps due to mechanisms such as axonal sprouting, synaptic enlargement, or synaptic ingrowth. In AD, however, the accelerated neuronal loss may overwhelm such compensatory mechanisms or alternatively, independent synaptic and perikaryal losses may occur.