NGF content in the cerebral cortex of non-demented patients with amyloid-plaques and in symptomatic Alzheimer's disease

There is increasing evidence that in Alzheimer's disease nerve growth facto r (NGF) protein and NGF mRNA content in post-mortem cortex is not decreased , but may even be elevated although the NGF-sensitive cholinergic basal for ebrain neurons are preferentially affected. However. only little is known a bout the early pathophysiological events leading to Alzheimer's disease. We therefore measured the post-mortem NGF concentrations in temporal and fron tal cortex of Alzheimer's disease patients, non-demented controls without A lzheimer's disease-related pathology, as well as non-demented patients with beta A4 plaques who might be classified as 'preclinical' cases. In the Alz heimer's disease group we found up to 43% increase in NGF concentrations in the frontal and temporal cortex as compared to the two other groups. In a subgroup analysis of the non-demented patients with plaques, NGF concentrat ions were lower in the frontal cortex when beta A4 plaques were present (46 % of the control temporal area) than in patients without evidence of fronta l plaques (81% of the control temporal area). This NGF decrease was paralle led to a similar decrease of choline acetyltransferase activity, which is r egulated by NGF in the cholinergic basal forebrain. These findings support the hypothesis of lower cortical NGF content at the onset of plaque formati on and of elevated NGF levels in the clinically manifest and neuropathologi cally advanced stage of the disease. (C) 1999 ISDN. Published by Elsevier S cience Ltd. All rights reserved.