Paradoxical Upregulation of Glutamatergic Presynaptic Boutons during Mild Cognitive Impairment
Open Access
- 3 October 2007
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 27 (40), 10810-10817
- https://doi.org/10.1523/jneurosci.3269-07.2007
Abstract
Synaptic integrity is now recognized as a central component of Alzheimer's disease. Surprisingly, however, the structural status of glutamatergic synapses in Alzheimer's disease is unclear, despite the fact that glutamate is the major excitatory transmitter of the CNS and has key roles in excitotoxicity and long-term potentiation. The identification of specific markers of glutamatergic neurons now allows an assessment of the structural involvement of the glutamatergic system across progressive stages of the Alzheimer's pathology, an opportunity not afforded by previously used neurochemical approaches. Glutamatergic presynaptic bouton density and dystrophic neurite abundance were quantified in midfrontal gyrus brain tissue from subjects with no cognitive impairment, mild cognitive impairment, or mild- or severe-stage Alzheimer's disease. Our study demonstrates a striking pathology-dependent pattern of glutamatergic synaptic remodeling with disease progression. Subjects with mild cognitive impairment display a paradoxical elevation in glutamatergic presynaptic bouton density, a situation akin to that observed in the cholinergic system, which then depletes and drops with disease progression. This pattern of synaptic remodeling mirrors our previous findings in transgenic animal models and is of major relevance to current transmitter-based therapeutics.Keywords
This publication has 55 references indexed in Scilit:
- Phosphorylation of Actin-Depolymerizing Factor/Cofilin by LIM-Kinase Mediates Amyloid -Induced Degeneration: A Potential Mechanism of Neuronal Dystrophy in Alzheimer's DiseaseJournal of Neuroscience, 2006
- Alzheimer's Disease Is a Synaptic FailureScience, 2002
- The pathology of Alzheimer's disease: Numbers countAnnals of Neurology, 1997
- The Role of Synaptic Proteins in the Pathogenesis of Disorders of the Central Nervous SystemBrain Pathology, 1993
- Immunohistochemical quantification of the synapse-related protein synaptophysin in Alzheimer diseaseNeuroscience Letters, 1989
- Presynaptic and postsynaptic glutamatergic function in Alzheimer's diseaseNeuroscience Letters, 1988
- Glutamatergic denervation in Alzheimer's disease--a cautionary note.Journal of Neurology, Neurosurgery & Psychiatry, 1987
- Region-specific loss of glutamate innervation in Alzheimer's diseaseNeuroscience Letters, 1987
- Clinical diagnosis of Alzheimer's diseaseNeurology, 1984
- Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia.BMJ, 1978