Co-Localization of Aluminium and Silicon in Senile Plaques: Implications for the Neurochemical Pathology of Alzheimer’s Disease

Abstract

The neuropsychiatric features of Alzheimer-type senile dementia (SDAT) are accompanied by a constellation of histopathological and biochemical abnormalities. At present, it is not known how the major structural changes associated with the disease such as senile plaques, neurofibrillary tangles (NFT) and granulovacuolar degeneration are related to the growing list of neurochemical deficits which have been reported in recent years. The latter include a reduction of neurotransmitters and related enzymes in the cholinergic, noradrenergic and serotoninergic pathways which project diffusely to the cortex from subcortical nuclei (for recent reviews, see Bowen et al. 1984; Bloxham et al. 1985; Hardy et al. 1985). Depletion of the cholinergic markers choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) are amongst the earliest and most severe of the biochemical changes to occur, and loss of these enzymes correlates well with the degree of cognitive impairment (Perry and Perry 1980). In addition to abnormalities in extrinsic cortical systems, there is also evidence for biochemical changes in intrinsic neurones. Thus, the level of immunoreactive somatostatin is reduced, especially in the temporal cortex, (for review, see Rossor et al. 1984), and there is a significant loss of cortical serotonin receptors (Cross et al. 1984). In addition, an increase in ³H-labelled glutamate binding in the caudate nucleus has been interpreted as the consequence of a loss of corticostriatal neurones which use this amino acid as a transmitter (see Davison et al., this volume).