Structural and Chemical Aspects of Cortical Pathology in Alzheimer’s Disease

Summary

In Alzheimer’s disease, which primarily involves memory disturbance, the neuropathological changes that occur may disrupt normal synaptic function. The presence of dystrophic nerve terminals associated with senile plaques in cortical areas involved with learning (especially the hippocampus and temporal neocortex) provides evidence of significant presynaptic disruption which increases with increasing plaque density. Such presynaptic abnormalities are reflected in the neurochemical deficits that occur in at least three extrinsic neurotransmitter systems in the cerebral cortex (cholinergic, noradrenergic and serotoninergic) in Alzheimer’s disease. The cholinergic deficit appears to be most closely correlated with the memory disturbance observed in both Alzheimer’s disease and Parkinson’s disease with dementia. Currently available evidence suggests that retrograde degeneration of the cortical cholinergic input may occur as a result of the neuropathological changes in Alzheimer’s disease, while in Parkinson’s disease with dementia where there are no marked neuropathological changes in the cortex, anterograde degeneration of the cholinergic system may occur. This focusses attention on the nature of senile plaques in relation to their ability to induce presynaptic dysfunction in Alzheimer’s disease. Elemental analysis shows that aluminium and silicon are present as aluminosilicates in the centre of plaque cores. Chemically active aluminosilicate species may be responsible for at least some of the presynaptic changes observed.