Reduction of cortical TrkA but not p75NTR protein in early‐stage Alzheimer's disease

  title={Reduction of cortical TrkA but not p75NTR protein in early‐stage Alzheimer's disease},
  author={Scott E. Counts and Muhammad Nadeem and Joanne Wuu and Stephen D. Ginsberg and H. Uri Saragovi and Elliott J. Mufson},
  journal={Annals of Neurology},
Degeneration of cholinergic nucleus basalis (NB) cortical projection neurons is associated with cognitive decline in late‐stage Alzheimer's disease (AD). NB neuron survival is dependent on coexpression of the nerve growth factor (NGF) receptors p75NTR and TrkA, which bind NGF in cortical projection sites. We have shown previously a significant reduction of NB perikarya expressing p75NTR and TrkA protein during the early stages of AD. Whether there is a concomitant reduction in cortical levels… 
Preservation of cortical sortilin protein levels in MCI and Alzheimer's disease
Down regulation of trk but not p75NTR gene expression in single cholinergic basal forebrain neurons mark the progression of Alzheimer's disease
Individual cholinergic NB neurons displayed a significant down regulation of trkA, trkB, and trkC expression during the progression of AD, suggesting trk defects may be a molecular marker for the transition from no cognitive impairment to MCI, and from MCI to frank AD.
Differential Expression of Synaptic Proteins in the Frontal and Temporal Cortex of Elderly Subjects With Mild Cognitive Impairment
The differential changes in DRB expression in the frontal and temporal cortex in MCI suggest a disparity of dendritic plasticity within these regions that may contribute to the early impairment of temporal cortical functions subserving memory and language compared with the relative preservation of frontal cortical executive function during the initial stages of cognitive decline.
The role of nerve growth factor receptors in cholinergic basal forebrain degeneration in prodromal Alzheimer disease.
Dysfunction of nerve growth factor (NGF) and its high (TrkA) and low (p75NTR) affinity receptors has been suggested to underlie the selective degeneration of the nucleus basalis (NB) cholinergic
Cholinotrophic molecular substrates of mild cognitive impairment in the elderly.
The concept that from a neurotrophic pathobiologic perspective, MCI is already early AD is supported, as there is a shift in cholinotrophic molecular events in MCI and early AD which may lead to cell dysfunction and eventual cell death over the course of the disease.
Progression of age‐associated cognitive impairment correlates with quantitative and qualitative loss of TrkA receptor protein in nucleus basalis and cortex
  • H. Saragovi
  • Biology, Psychology
    Journal of neurochemistry
  • 2005
A direct correlation between disease progression and reduced expression of TrkA receptor in cholinergic neurons has been documented in neurocognitive pathologies including Alzheimer's disease. We
Shift in the Balance of TRKA and ProNGF in Prodromal Alzheimer ’s Disease
To better understand the roles of NGF, proNGF, the common neurotrophin receptor p75, and the high-affinity trkA receptor in basal cortical dysfunction and their relation to cognitive impairment, postmortem brain tissue from subjects during the prodromal stages of AD is examined.
Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications
Drugs treating the multiple pathologies and clinical symptoms in AD (e.g., M1 cholinoceptor and/or galaninergic drugs) should be considered for a more comprehensive treatment approach for cholinergic dysfunction.
Increased Matrix Metalloproteinase 9 Activity in Mild Cognitive Impairment
Examining human frontal and parietal cortex tissues from aged subjects with a clinical diagnosis of AD, mild cognitive impairment, or no cognitive impairment suggested that a reduction in mNGF as a consequence of MMP-9-mediated degradation may in part underlie the pathogenesis of cognitive deficits in mild Cognitive impairment and AD.


Loss of basal forebrain P75NTR immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease
Examination of the expression of the low affinity p75 neurotrophin receptor (p75NTR), an excellent marker of CBF neurons, in postmortem tissue derived from clinically well‐characterized individuals who have been classified as having no cognitive impairment, mild cognitive impairment (MCI), and mild AD supports the concept that phenotypic changes, but not frank neuronal degeneration, occur early in cognitive decline.
Reduction in p140-TrkA Receptor Protein within the Nucleus Basalis and Cortex in Alzheimer's Disease
A significant reduction in trkA protein is revealed within both the nucleus basalis and the frontal cortex in AD relative to aged controls, which supports the concept that defects in the production and/or utilization of thetrkA receptor may be a key event mediating degeneration of NGF-responsive CBF neurons in this disease.
Increased proNGF Levels in Subjects with Mild Cognitive Impairment and Mild Alzheimer Disease
It is demonstrated that proNGF levels increase during the preclinical stage of AD and may reflect an early biological marker for the onset of AD.
Preservation of brain nerve growth factor in mild cognitive impairment and Alzheimer disease.
Brain NGF levels appear sufficient to support the cholinergic plasticity changes seen in MCI and remain stable throughout the disease course.
Nerve growth factor in Alzheimer's disease: increased levels throughout the brain coupled with declines in nucleus basalis
The present findings indicate that AD is characterized by a widespread increase in cortical and subcortical NGF, and the AD-related decline in NGF found in nbM is consistent with the possibility of impaired retrograde transport of NGF to this region.
Loss of nucleus basalis neurons containing trkA immunoreactivity in individuals with mild cognitive impairment and early Alzheimer's disease
Data indicate that alterations in the number of nucleus basalis neurons containing trkA immunoreactivity occurs early and are not accelerated from the transition from MCI to mild AD.
Preservation of nucleus basalis neurons containing choline acetyltransferase and the vesicular acetylcholine transporter in the elderly with mild cognitive impairment and early Alzheimer's disease
The data suggest that cholinergic neurons, and the coexpression of ChAT and VAChT, are relatively preserved in early stages of AD.
Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment
Autopsy data indicate that atrophy and loss of layer II entorhinal cortex neurons occur in elderly subjects with mild cognitive impairment prior to the onset of dementia and suggests that these changes are not exacerbated in early Alzheimer's disease.