The neuroanatomy of the reticular nucleus locus coeruleus in Alzheimer’s disease

Filippo S. Giorgi, Larisa Ryskalin, Riccardo Ruffoli, Francesca Biagioni, Fiona Limanaqi, Michela Ferrucci, Carla L. Busceti, Ubaldo Bonuccelli, Francesco Fornai

Research output: Contribution to journalShort survey

Abstract

Alzheimer’s Disease (AD) features the accumulation of b-amyloid and Tau aggregates, which deposit as extracellular plaques and intracellular neurofibrillary tangles (NFTs), respectively. Neuronal Tau aggregates may appear early in life, in the absence of clinical symptoms. This occurs in the brainstem reticular formation and mostly within Locus Coeruleus (LC), which is consistently affected during AD. LC is the main source of forebrain norepinephrine (NE) and it modulates a variety of functions including sleepwaking cycle, alertness, synaptic plasticity, and memory. The iso-dendritic nature of LC neurons allows their axons to spread NE throughout the whole forebrain. Likewise, a prion-like hypothesis suggests that Tau aggregates may travel along LC axons to reach out cortical neurons. Despite this timing is compatible with cross-sectional studies, there is no actual evidence for a causal relationship between these events. In the present mini-review, we dedicate special emphasis to those various mechanisms that may link degeneration of LC neurons to the onset of AD pathology. This includes the hypothesis that a damage to LC neurons contributes to the onset of dementia due to a loss of neuroprotective effects or, even the chance that, LC degenerates independently from cortical pathology. At the same time, since LC neurons are lost in a variety of neuropsychiatric disorders we considered which molecular mechanism may render these brainstem neurons so vulnerable.

Original languageEnglish
Article number80
JournalFrontiers in Neuroanatomy
Volume11
DOIs
Publication statusPublished - Sep 19 2017

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Keywords

  • Amyloid
  • Basal forebrain nuclei
  • Mild cognitive impairment
  • Neurofibrillary tangles
  • Phospho-Tau
  • Pre-clinical AD

ASJC Scopus subject areas

  • Anatomy
  • Neuroscience (miscellaneous)
  • Cellular and Molecular Neuroscience

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