Functional Consequences of Locus Coeruleus Degeneration in Alzheimers Disease

Abstract

Alzheimer's disease (AD) is the most common cause of cognitive impairment in older patients, and its prevalence is expected to soar in coming decades. Neuropathologically, AD is characterized by beta-amyloid-containing plaques, tau-containing neurofibrillary tangles, and cholinergic neuronal loss. In addition to the hallmark of memory loss, the disease is associated with other neuropsychiatric and behavioral abnormalities, including psychosis, aggression, and depression. Although cholinergic cell loss is clearly an important attribute of the pathological process, another well-described yet underappreciated early feature of AD pathogenesis is degeneration of the locus coeruleus (LC), which serves as the main source of norepinephrine (NE) supplying various cortical and subcortical areas that are affected in AD. The purpose of this review is to explore the extent to which LC loss contributes to AD neuropathology and cognitive deficits.

Evaluation of Parkinson Disease and Alzheimer Disease with the Use of Neuromelanin MR Imaging and123I-Metaiodobenzylguanidine Scintigraphy

“…7 Some reports suggest that a reduction in the number of noradrenergic neurons affects the accumulation of ␤-amyloid, inflammation, or microcirculation in the LC. 23,24 Our NmMRI study could not identify a significant signal reduction in the LC of patients with Alzheimer disease. Busch et al 25 reported that the LC begins to lose cells only during the later stages of Alzheimer disease.…”

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

“…Interestingly, LC cell death is either very limited or nonexistent in transgenic mice models of Alzheimer's disease [115]. Thus, in the next part of our study we applied knockout mice for different SST receptors (SSTR1, 2, 4) and their wild-type littermates, to further study a potential role of SSTR2 signalling in the maintenance of the noradrenergic system.…”

“…The currently used mouse models of Alzheimer's disease (transgenic mice expressing mutant forms of amyloid precursor protein (APP), presenilins and tau, singly or in combination), however, exhibit at most mild LC degeneration or no degeneration at all [115,45]. In contrast, a selective.…”

Norepinephrine Promotes Microglia to Uptake and Degrade Amyloid β Peptide through Upregulation of Mouse Formyl Peptide Receptor 2 and Induction of Insulin-Degrading Enzyme

“…In AD patients the central portion of the LC, which is considered to project predominantly to the hippocampus, frontal and temporal cortex areas that are usually severely affected by senile plaque and neurofibrillary tangle formation, shows the most extensive loss of cells (Marcyniuk et al, 1986). The decreased LC neuron numbers are significantly correlated with the increase of amyloid plaques, neurofibrillary tangles, and severity of dementia (Marcyniuk et al, 1986;Bondareff et al, 1987;Grudzien et al, 2007;Weinshenker, 2008). In rodent AD models, neurotoxin N-(2-chloroethyl)-N-ethyl-bromobenzylamine (DSP4)-induced LC neuron degeneration and NE deficiency exacerbate A␤ deposition, inflammation, neurodegeneration in brain, and cognitive impairment (Heneka et al, 2006;Kalinin et al, 2007).…”