Reduced Numbers of Somatostatin Receptors in the Cerebral Cortex in Alzheimer's Disease

Abstract

Somatostatin receptor concentrations were measured in patients with Alzheimer's disease and controls. In the frontal cortex (Brodmann areas 6, 9, and 10) and temporal cortex (Brodmann area 21), the concentrations of somatostatin in receptors in the patients were reduced to approximately 50 percent of control values. A 40 percent reduction was seen in the hippocampus, while no significant changes were found in the cingulate cortex, postcentral gyrus, temporal pole, and superior temporal gyrus. Scatchard analysis showed a reduction in receptor number rather than a change in affinity. Somatostatin-like immunoreactivity was significantly reduced in both the frontal and temporal cortex. Somatostatin-like immunoreactivity was linearly related to somatostatin-receptor binding in the cortices of Alzheimer's patients. These findings may reflect degeneration of postsynaptic neurons or cortical afferents in the patients' cerebral cortices. Alternatively, decreased somatostatin-like immunoreactivity in Alzheimer's disease might indicate increased release of somatostatin and down regulation of postsynaptic receptors.

Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: a quantitative study of visual and auditory cortices

“…1. The prosomatostatin-derived peptide (PSDP) system of the cortex is profoundly altered in AD, as reflected in decreased tissue levels of PSDP (Davies et al, 1980;Rossor et al, 1980), the presence of PSDP-immunoreactive profiles in NP Morrison et al, 1985) and a reduction in PSDP receptor number (Beal et al, 1985). Although these findings might suggest that there is a loss of PSDP-containing cortical neurons in AD, the density of cortical PSDP-containing neurons has recently been reported to be normal in this disorder (Nakamura and Vincent, 1986).…”

Minocycline provides protection against β-amyloid(25-35)-induced alterations of the somatostatin signaling pathway in the rat temporal cortex

“…Among the numerous neuropeptides produced in intrinsic cortical and hippocampal neurons, SRIF has been found to be the most consistently reduced in the brain and cerebrospinal fluid of AD patients (Davies et al, 1980;Beal et al, 1986;Nemeroff et al, 1992;Bissette et al, 1998;BurgosRamos et al, 2008). SRIF receptors are also markedly depleted in the AD brain (Beal et al, 1985), there being subtype-selective alterations in cortical areas (Kumar, 2005). AD is characterized clinically by progressive dementia and, histopathologically, by the presence of extracellular deposits of amyloid fibrils in the core of senile plaques, intracellular neurofibrillar tangles and neuronal cell loss (Braak and Braak, 1991;Selkoe, 2001).…”

Somatostatin and Alzheimer's disease

“…The SRIF receptor concentration was unaltered in the cingulate cortex, hippocampus and postcentral gyrus. The correlation between reduced SRIF-LI and reduced SSTRs in the same cortical areas of AD patients could reflect loss of both presynaptic (SRIF) and postsynaptic (SRIFceptiv) neurons in areas which are predisposed to the pathologic process (Beal et al, 1985). In contrast, Withford et al (1988) found no changes in the SRIF receptor density in AD brain; this discrepancy is most likely attributable to differences in the severity of the cases analyzed.…”

“…Initial studies by Beal et al (1985) in the AD post-mortem brain revealed a dramatic reduction of approximately 50% in the SRIF receptor density, as compared to age-matched control brains, in the frontal cortex (Brodman areas 6, 9 and 10) and temporal cortex (Brodman area 21), regions where the SRIF deficit is also most notable. No changes, however, were detected in the SRIF receptor affinity in any of these cortical areas.…”