Glutamatergic synapses undergo remodeling during AD progression
Original article
Bell KFS et al. (2007) Paradoxical upregulation of glutamatergic presynaptic boutons during mild cognitive impairment. J Neurosci 27: 10810–10817 PubMed
Synaptic density is emerging as a factor that correlates closely with cognitive status in Alzheimer's disease (AD). Glutamatergic synapses in the cortex and hippocampus might be particularly important in the pathology of AD. Bell et al. have now shown that these synapses undergo substantial remodeling during AD progression, including an unexpected upregulation of glutamatergic presynaptic bouton density in patients with mild cognitive impairment.
The authors investigated whether specific markers for glutamatergic neurons can provide more information than traditional neurochemical investigations about the glutamatergic pathology associated with AD. Antibodies highly specific for the vesicular glutamate transporter 1 were used to identify glutamatergic presynaptic elements (boutons) and glutamatergic dystrophic neurites in post mortem midfrontal gyrus brain tissue from participants of the Religious Orders Study, a longitudinal study of aging and AD.
AD pathology was shown to include the generation of glutamatergic dystrophic neurites, which reduces synaptic connectivity, thereby contributing to cognitive decline. As expected, glutamatergic presynaptic boutons were significantly depleted in samples from men and women with mild and severe AD, compared with controls. Increased glutamatergic presynaptic bouton density in each group correlated with improved cognition, except in individuals with mild cognitive impairment. Paradoxically, glutamatergic presynaptic bouton density was elevated in the patients with mild cognitive impairment; the density then dropped as the patients progressed to AD.
The authors conclude that compensatory upregulation of cortical terminals might occur during the mild cognitive impairment that is prodromic of AD. They suggest that this period represents a potential therapeutic window within which some of the subsequent neuronal damage that occurs during AD progression can be delayed.
Contact the journal about this article
Subject areas under which this article appears: Aging and dementia