Protein Kinases and Growth Associated Proteins in Plaque Formation in Alzheimer's Disease

The purpose of this review is to analyze recent developments in the study of the role of second and third intracellular messengers in plaque formation in Alzheimer's disease (AD). We review recent results from in vitro, in vivo, and autopsy studies that support a possible role of altered protein kinase C (PKC) function in the pathogenesis of plaque formation in the AD brain. PKC could be involved in plaque formation either by inducing aberrant sprouting by abnormally processing growth related substrates such as amyloid precursor protein (APP) and growth-associated protein 43 (GAP-43), or by leading to neurodegeneration and synaptic loss due to decreased activity in association with amyloid deposition in the plaque. A unified hypothesis is proposed where cycles of sprouting and neurodegeneration (degeneration by overstimulation) could be the central mechanism by which altered PKC and growth related molecules induce plaque formation in AD.

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