Oestrogen and nerve growth factor – neuroprotection and repair in Alzheimer’s disease

Abstract

The neurogenetics and neuropathology of Alzheimer's disease (AD) are still largely unknown, even though recent work has clarified some genetic components in this common and devastating neurodegenerative disease. Most of the genetic mutations have been shown to be, at least in the early onset type of AD, related to the function of a large transmembrane protein, amyloid precursor protein (APP). This protein is cleaved into various smaller fragments that are either soluble or aggregating. It is thought that this processing of APP is inherently important for the initiation and progression of AD. Recent animal models have suggested that it is not the formation of beta-amyloid plaques per se, but the altered processing of APP and the subsequent loss of soluble APP, that sets the stage for the massive neuronal cell loss which occurs in AD. We would like to propose a three-way relationship between oestrogen, APP and nerve growth factor (NGF) in the neural pathways of the brain which are involved in learning and memory - the limbic system. The degeneration of the cholinergic innervation from the basal forebrain to the hippocampal formation in the temporal lobe is thought to be one of the factors determining the progression of memory decay, both during normal ageing and AD. Oestrogen and NGF are among the neuroprotective agents that have shown some potential for the treatment of AD. Previous results of treatment with these two agents and their relationship to the amyloid proteins, will be discussed in this review.