Increased plasma bradykinin level is associated with cognitive impairment in Alzheimer's patients.
Alzheimer's disease
Beta-amyloid
Bradykinin
Cognitive impairment
Contact activation system
High molecular weight kininogen
Inflammation
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
09
12
2019
revised:
28
02
2020
accepted:
11
03
2020
pubmed:
17
3
2020
medline:
13
4
2021
entrez:
17
3
2020
Statut:
ppublish
Résumé
Alzheimer's disease (AD) is characterized by the presence of proteinaceous brain deposits, brain atrophy, vascular dysfunction, and chronic inflammation. Along with cerebral inflammation, peripheral inflammation is also evident in many AD patients. Bradykinin, a proinflammatory plasma peptide, is also linked to AD pathology. For example, bradykinin infusion into the hippocampus causes learning and memory deficits in rats, and blockade of the bradykinin receptor lessens cognitive impairment in AD mouse models. Even though it has been hypothesized that plasma bradykinin could contribute to inflammation in AD, the level of plasma bradykinin and its association with beta-amyloid (Aβ) pathology in AD patients had not been explored. Here, we assessed plasma bradykinin levels in AD patients and age-matched non-demented (ND) control individuals. We found significantly elevated plasma bradykinin levels in AD patients compared to ND subjects. Additionally, changes in plasma bradykinin levels were more profound in many AD patients with severe cognitive impairment, suggesting that peripheral bradykinin could play a role in dementia most likely via inflammation. Bradykinin levels in the cerebrospinal fluid (CSF) were reduced in AD patients and exhibited an inverse correlation with the CSF Aβ40/Aβ42 ratio. We also report that bradykinin interacts with the fibrillar form of Aβ and co-localizes with Aβ plaques in the post-mortem human AD brain. These findings connect the peripheral inflammatory pathway to cerebral abnormalities and identify a novel mechanism of inflammatory pathology in AD.
Identifiants
pubmed: 32173555
pii: S0969-9961(20)30108-X
doi: 10.1016/j.nbd.2020.104833
pmc: PMC7175647
mid: NIHMS1579676
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Apolipoproteins E
0
Biomarkers
0
Bradykinin
S8TIM42R2W
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104833Subventions
Organisme : NINDS NIH HHS
ID : R01 NS102721
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS106668
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None
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