Somatostatin immunoreactivity in neuritic plaques of Alzheimer's patients

Abstract

Senile dementia of the Alzheimer's type can be diagnosed with certainty only by examining neurofibrillary tangles and neuritic plaques under the microscope. Recently, it has been suggested that the condition is linked to specific neurotransmitter systems, with a decline of cortical acetylcholine, choline acetyltransferase, cholinergic neurones projecting to the cortex, cortical noradrenaline content, locus coeruleus neurones and cortical somatostatic content. Using immunocytochemical methods, we here report that somatostatin-immunoreactive processes are present in neuritic plaques in human Alzheimer's specimens. These data, as well as other reports of non-cholinergic changes, strongly imply that Alzheimer's disease cannot be linked exclusively to cortical cholinergic elements, as proposed previously. Rather, our data on plaque and somatostatin co-localization and distribution patterns suggest that Alzheimer's neuropathology may involve primarily the loss of selective cortical neurones that are targets of the implicated transmitter systems and that plaque formation may result from the degeneration of presynaptic and postsynaptic neurites of large projection neurones in layers III and V. Given the neurochemically heterogeneous input to these cells, it is not surprising that several neurotransmitter systems, one of which is somatostatin, are implicated in the pathology of Alzheimer's disease.

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).…”

“…Cholinergic and catecholaminergic processes, presumably the terminations of afferents from the brain stem, have been identified in simian and human cortical NP (Kitt et al, 1984(Kitt et al, , 1985Armstrong et al, 1986). NP-containing fibers immunoreactive for a number of different neuropeptides such as PSDP Morrison et al, 1985) neuropeptide Y (Chan-Palay et al, 1985;, and substance P have also been described in the neocortex from patients with AD. Thus, NP may arise at the terminations of long corticocortical projection neurons, at the terminations of various afferent fibers from the brain stem, such as those from cholinergic or noradrenergic neurons, and from the processes of intrinsic cortical neurons, such as those containing PSDP.…”

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

“…First, SST-NPY containing interneurons have been implicated in learning and memory [93][94][95][96] and post-mortem brain studies of AD repeatedly observed a severe loss of SST immunoreactive neurons and axons. 31,95,[97][98][99][100] In addition, APPswe/PS1dE9 amyloid plaque producing mice show reduced SST levels in the cortex, 101 and this is likely mediated through the interference of amyloid-beta (Ab) with the BDNF-induced activation of the Ras-mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3-K)/Akt pathways. 102 In contrast, it appears that inducing increased expression of SST may be beneficial for patients suffering from AD: compounds increasing SST expression are in phase II clinical trials as cognition enhancing agents (FK962, Astellas Pharma, Tokyo, Japan), 103 and transgenic models of amyloid deposition are reversed by environmental enrichment, 25 which is known to induce SST-NPY expression via a BDNF-dependent pathway.…”

Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system: new aspects on Alzheimer’s disease

“…Likewise, SSTR2 mRNA expression was significantly decreased in the frontal and temporal cortices [42,59]. Amyloid plaques show immunoreactivity for SST [74]. Also, polymorphisms of the SST gene are risks factors for Alzheimer's disease [111,117], albeit not confirmed in genome-wide association studies (GWAS).…”