NGF content in the cerebral cortex of non-dementedpatients with amyloid-plaques and in symptomaticALZHEIMER S disease

Abstract

There is increasing evidence that in Alzheimers disease nerve growth factor (NGF)protein and NGF mRNA content in post-mortem cortex is not decreased, but may evenbe elevated although the NGF-sensitive cholinergic basal forebrain neurons are preferentiallyaffected. However, only little is known about the early pathophysiological events leading toAlzheimers disease. We therefore measured the post-mortem NGF concentrations intemporal and frontal cortex of Alzheimers disease patients, non-demented controls withoutAlzheimers disease-related pathology, as well as non-demented patients with βA4plaques who might be classified as preclinical cases. In the Alzheimers disease group we found upto 43% increase in NGF concentrations in the frontal and temporal cortex as compared to the twoother groups. In a subgroup analysis of the non-demented patients with plaques, NGFconcentrations were lower in the frontal cortex when βA4 plaques were present (46% ofthe control temporal area) than in patients without evidence of frontal plaques (81% of the controltemporal area). This NGF decrease was paralleled to a similar decrease of cholineacetyltransferase activity, which is regulated by NGF in the cholinergic basal forebrain. Thesefindings support the hypothesis of lower cortical NGF content at the onset of plaque formationand of elevated NGF levels in the clinically manifest and neuropathologically advanced stage ofthe disease.