Nerve growth factor receptors in a brain damaged by Alzheimers

Hefti et al., hypothesized that the specific brain areas that nerve growth factor receptors reside in would differ in a typical aged human brain, when compared to that of a patient with Alzheimers disease. Nerve growth factors are essential for multiple brain functions, including memory and various cognitive performance and abilities.  Hefti et al., deemed the localization of nerve growth factor receptors especially important due to the receptors relationship with cholinergic neurons, acting as a neurotrophic factor. Mufson et al., later established a correlation present between decreased representation of nerve growth factor receptors in various sectors of the basal forebrain in patients with Alzheimers disease compared to those of controls.

Mufson et al., proposed that contrary to previous findings, a problem in binding, and or transporting of NGF could be causing retrograde transport to the nucleus basalis to be insufficient. The brains of patients with Alzheimers disease were compared to brains of those with typical neurology, which were used as controls. Each brain was sliced, treated, and stained in order to identify the quantity of NGF receptors in a given location. Mufson et al., observed the largest absence of nerve growth factor receptors located in the Ch4 region of the basal forebrain of AD patients, the region being described as having the most significant loss of NGF receptor-immunoreactive neurons compared to that of Ch1-Ch2.

Observations by Hefti et al., confirm that NGF receptors were isolated in the basal forebrain cholinergic neurons of the human brain, noting a densely packed region of NGF receptor positive neurons in neurologically typical brains. Confirming this finding, Mufson et al., discovered that the visible concentration of NGF in AD patients was found to be significantly reduced compared to that of age matched controls. The findings of Hefti et al., solidified that NGF receptor immunohistochemistry is a dependable method of locating basal forebrain cholinergic neurons located in the adult human brain.

Hefti et al., observed that as normal aging progressed, the density of NGF receptors decreased, in addition, the amount of NGF receptor positive cells in patients with Alzheimers disease was reduced. These findings were supported by Mufson et al., which observed significant depletion of NGF receptor-containing neurons in the nucleus basalis. In contrast, no loss was detected in the hippocampal regions of AD patients.

The findings of Mufson et al., have suggested that the lack of NGF receptors in AD patients reflects the death of neurons rather than a deficiency of neurons located in the basal forebrain to synthesize and express NGF receptors. Mufson et al., later discovered that cholinergic basal forebrain neurons of AD patients have a reduced ability to acquire NGF, compared to those of aged matched controls. The findings of Mufson et al., proposed a lack of trophic support for CBF neurons in AD patients, further causing inadequate NGF accumulation. Therefore causing possible restricted NGF binding, as well as retrograde transport to CBF.

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