Title:Locus (Coeruleus) Minoris Resistentiae in Pathogenesis of Alzheimer’s Disease
Volume: 11
Issue: 10
Author(s): Boris Mravec, Katarina Lejavova and Veronika Cubinkova
Affiliation:
Keywords:
Alzheimer's disease, blood-brain-barrier, locus coeruleus, neuroinflammation, plasticity, tau protein.
Abstract: Alzheimer’s disease (AD) represents the most prevalent form of dementia in the elderly. However, the pathological
mechanisms underlying the development and progression of AD are only partially understood. To date, the accumulated
clinical and experimental evidence indicate that the locus coeruleus (LC), the main source of brain’s norepinephrine,
represents “the epicenter” of pathology leading to the development of AD. Evidence for this includes observations
that neurons of the LC modulate several processes that are altered in brains of AD patients, including synaptic plasticity,
neuroinflammation, neuronal metabolism, and blood-brain-barrier permeability. Moreover, the LC undergoes significant
degeneration in the brains of AD patients and is considered a source of the prion-like spreading of tau pathology to forebrain
structures innervated by the noradrenergic neurons of the LC. Furthermore, lesions of the LC exaggerate AD-related
pathology, while augmentation of the brain’s noradrenergic neurotransmission reduces both neuroinflammation and cognitive
decline. We hypothesize that better understanding the role of the LC neurons in AD pathogenesis may lead to development
of new strategies for the treatment of AD.
