Neuron in Alzheimer’s disease

There are two main hypotheses to explain the damage to neurones in Alzheimer s disease ... 

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NGF is secreted by neurones in the hippocampus and is transported via the fimbria fornix to basal forebrain cholinergic neurones. In Alzheimer s disease, a disruption in NGF production could explain the degenerations of the nucleus basalts of Meynert. In Alzheimer s disease, neurones are only lost from the rostral part of the locus ceruleus where neurones are responsive to cortical neurotrophic factors [85], Actually, it appears that NGF production in the brain of patients with Alzheimer s disease is normal. Inversely, decreased expression of brain-derived neurotrophic factor (BDNF) has been detected in post-mortem Alzheimer patients brains. Furthermore, NGF receptor density has been shown to be significantly reduced. Loss of neurotrophin receptors may result in neuronal degeneration, as available factors are unable to convey trophic support to dependent neurones. In addition, possible interactions between trophic factors and amyloid protein deposits have been investigated. Administered in vitro, NGF would potentiate -amyloid neurotoxicity. The gamma subunit of the 75 NGF complex appears to possess peptidase activity and could contribute to APP mis-metabo-lism [86]. 

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Finally, it should be noted that not only are KSPGs present in the normal brain, associated with most neurons of the cerebral cortex, for example, but also that the epitope for highly sulfated KS chains disappears from these neurons in Alzheimer s disease [55]. However, the periphery of Alzheimer s disease neuritic plaques is positive for KS [56]. 

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