PMID- 35052606
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220128
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Dec 31
TI  - A Leaky Blood-Brain Barrier to Fibrinogen Contributes to Oxidative Damage in 
      Alzheimer's Disease.
LID - 10.3390/antiox11010102 [doi]
LID - 102
AB  - The intactness of blood-brain barrier (BBB) is compromised in Alzheimer's disease 
      (AD). Importantly, evidence suggests that the perturbation and abnormalities 
      appearing in BBB can manifest early in the progression of the disease. The 
      disruption of BBB allows extravasation of the plasma protein, fibrinogen, to 
      enter brain parenchyma, eliciting immune reactivity and response. The presence of 
      amyloid-beta (Abeta) peptide leads to the formation of abnormal aggregates of fibrin 
      resistant to degradation. Furthermore, Abeta deposits act on the contact system of 
      blood coagulation, altering levels of thrombin, fibrin clots and 
      neuroinflammation. The neurovascular unit (NVU) comprises an ensemble of brain 
      cells which interact with infiltrating fibrinogen. In particular, interaction of 
      resident immune cell microglia with fibrinogen, fibrin and Abeta results in the 
      production of reactive oxygen species (ROS), a neurotoxic effector in AD brain. 
      Overall, fibrinogen infiltration through a leaky BBB in AD animal models and in 
      human AD tissue is associated with manifold abnormalities including persistent 
      fibrin aggregation and clots, microglial-mediated production of ROS and 
      diminished viability of neurons and synaptic connectivity. An objective of this 
      review is to better understand how processes associated with BBB leakiness to 
      fibrinogen link vascular pathology with neuronal and synaptic damage in AD.
FAU - McLarnon, James G
AU  - McLarnon JG
AD  - Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, 
      The University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC 
      V6T1Z3, Canada.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20211231
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC8772934
OTO - NOTNLM
OT  - amyloid-beta peptide
OT  - blood-brain barrier
OT  - fibrin aggregation and clots
OT  - fibrinogen
OT  - microglia
OT  - neurodegeneration
OT  - neurovascular unit
OT  - reactive oxygen species
COIS- The author declares no conflict of interest.
EDAT- 2022/01/22 06:00
MHDA- 2022/01/22 06:01
PMCR- 2021/12/31
CRDT- 2022/01/21 01:03
PHST- 2021/12/08 00:00 [received]
PHST- 2021/12/26 00:00 [revised]
PHST- 2021/12/28 00:00 [accepted]
PHST- 2022/01/21 01:03 [entrez]
PHST- 2022/01/22 06:00 [pubmed]
PHST- 2022/01/22 06:01 [medline]
PHST- 2021/12/31 00:00 [pmc-release]
AID - antiox11010102 [pii]
AID - antioxidants-11-00102 [pii]
AID - 10.3390/antiox11010102 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2021 Dec 31;11(1):102. doi: 10.3390/antiox11010102.