Alzheimer's Disease (AD) represents the main degenerative dementia. Its neuropathological hallmarks are β-amyloid plaques (APs) and neurofibrillary tangles (NFT), which lead to neuronal loss and brain atrophy. Recent data show that, early in the course of AD, hyperphosphorylated Tau proteins accumulate in Locus Coeruleus (LC) neuronal bodies. The fact that similar alterations have been found also in the entorhinal cortex suggests a causal relationship, although no final causal evidence exists. Later on, in the course of the disease, frank LC neuronal loss occurs, which is associated with marked cerebral NE reduction. In AD, neuroinflammation plays a pivotal role early in the process of APs deposition. LC degeneration is likely to play a key role in AD pathogenesis. In fact, NE modulates growth factors expression as well as integrity and functioning of the blood-brain barrier, and it also directly affects neuroinflammation. For instance, LC modulates microglia and astrocyte function, and this is evident following damage to LC, which induces astro- and micro-gliosis around APs, as well as interleukins secretion. These phenomena are dependent on the activation of beta-adrenergic receptors. The present review provides evidence about immune-mediated mechanisms through which LC may impact the course of AD. Some findings are consolidated in animal models. Should these data be confirmed in humans, adrenergic agents might represent potential therapeutic approaches acting on neuroinflammation to slow down the progression of AD.
|Number of pages||12|
|Journal||Brain Research Bulletin|
|Publication status||Published - Nov 2019|