PMID- 32875628
OWN - NLM
STAT- MEDLINE
DCOM- 20210917
LR  - 20210917
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Linking)
VI  - 98
IP  - 12
DP  - 2020 Dec
TI  - Locus Coeruleus and neurovascular unit: From its role in physiology to its 
      potential role in Alzheimer's disease pathogenesis.
PG  - 2406-2434
LID - 10.1002/jnr.24718 [doi]
AB  - Locus coeruleus (LC) is the main noradrenergic (NA) nucleus of the central 
      nervous system. LC degenerates early during Alzheimer's disease (AD) and NA loss 
      might concur to AD pathogenesis. Aside from neurons, LC terminals provide dense 
      innervation of brain intraparenchymal arterioles/capillaries, and NA modulates 
      astrocyte functions. The term neurovascular unit (NVU) defines the strict 
      anatomical/functional interaction occurring between neurons, glial cells, and 
      brain vessels. NVU plays a fundamental role in coupling the energy demand of 
      activated brain regions with regional cerebral blood flow, it includes the 
      blood-brain barrier (BBB), plays an active role in neuroinflammation, and 
      participates also to the glymphatic system. NVU alteration is involved in AD 
      pathophysiology through several mechanisms, mainly related to a relative 
      oligoemia in activated brain regions and impairment of structural and functional 
      BBB integrity, which contributes also to the intracerebral accumulation of 
      insoluble amyloid. We review the existing data on the morphological features of 
      LC-NA innervation of the NVU, as well as its contribution to neurovascular 
      coupling and BBB proper functioning. After introducing the main experimental data 
      linking LC with AD, which have repeatedly shown a key role of neuroinflammation 
      and increased amyloid plaque formation, we discuss the potential mechanisms by 
      which the loss of NVU modulation by LC might contribute to AD pathogenesis. 
      Surprisingly, thus far not so many studies have tested directly these mechanisms 
      in models of AD in which LC has been lesioned experimentally. Clarifying the 
      interaction of LC with NVU in AD pathogenesis may disclose potential therapeutic 
      targets for AD.
CI  - (c) 2020 Wiley Periodicals LLC.
FAU - Giorgi, Filippo Sean
AU  - Giorgi FS
AUID- ORCID: 0000-0002-2940-8128
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, University of Pisa, Pisa, Italy.
AD  - Neurology Unit, Pisa University Hospital, Pisa, Italy.
FAU - Galgani, Alessandro
AU  - Galgani A
AD  - Neurology Unit, Pisa University Hospital, Pisa, Italy.
FAU - Puglisi-Allegra, Stefano
AU  - Puglisi-Allegra S
AD  - I.R.C.C.S. I.N.M. Neuromed, Pozzilli, Italy.
FAU - Limanaqi, Fiona
AU  - Limanaqi F
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, University of Pisa, Pisa, Italy.
FAU - Busceti, Carla Letizia
AU  - Busceti CL
AD  - I.R.C.C.S. I.N.M. Neuromed, Pozzilli, Italy.
FAU - Fornai, Francesco
AU  - Fornai F
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, University of Pisa, Pisa, Italy.
AD  - I.R.C.C.S. I.N.M. Neuromed, Pozzilli, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200901
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
SB  - IM
MH  - Alzheimer Disease/immunology/pathology/*physiopathology
MH  - Animals
MH  - Blood-Brain Barrier/immunology/pathology/*physiopathology
MH  - Humans
MH  - Locus Coeruleus/pathology/*physiology
MH  - Neurovascular Coupling/*physiology
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - astrocytes
OT  - blood-brain barrier
OT  - locus coeruleus
OT  - neuroinflammation
OT  - neurovascular coupling
OT  - neurovascular unit
OT  - noradrenaline
EDAT- 2020/09/03 06:00
MHDA- 2021/09/18 06:00
CRDT- 2020/09/03 06:00
PHST- 2020/05/14 00:00 [received]
PHST- 2020/06/26 00:00 [revised]
PHST- 2020/08/08 00:00 [accepted]
PHST- 2020/09/03 06:00 [pubmed]
PHST- 2021/09/18 06:00 [medline]
PHST- 2020/09/03 06:00 [entrez]
AID - 10.1002/jnr.24718 [doi]
PST - ppublish
SO  - J Neurosci Res. 2020 Dec;98(12):2406-2434. doi: 10.1002/jnr.24718. Epub 2020 Sep 
      1.