Blood-Brain Barrier Breakdown in Relationship to Alzheimer and Vascular Disease.
Aged
Alzheimer Disease
/ cerebrospinal fluid
Amyloid beta-Peptides
/ cerebrospinal fluid
Blood-Brain Barrier
/ diagnostic imaging
Capillary Permeability
/ physiology
Cognitive Dysfunction
/ cerebrospinal fluid
Cross-Sectional Studies
Female
Humans
Magnetic Resonance Imaging
/ methods
Male
Middle Aged
Peptide Fragments
/ cerebrospinal fluid
Serum Albumin, Human
/ cerebrospinal fluid
Vascular Diseases
/ cerebrospinal fluid
tau Proteins
/ cerebrospinal fluid
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
04
05
2021
received:
28
01
2021
accepted:
15
05
2021
pubmed:
28
5
2021
medline:
9
11
2021
entrez:
27
5
2021
Statut:
ppublish
Résumé
Blood-brain barrier (BBB) breakdown has been suggested to be an early biomarker in human cognitive impairment. However, the relationship between BBB breakdown and brain pathology, most commonly Alzheimer disease (AD) and vascular disease, is still poorly understood. The present study measured human BBB function in mild cognitive impairment (MCI) patients on 2 molecular scales, specifically BBB's permeability to water and albumin molecules. Fifty-five elderly participants were enrolled, including 33 MCI patients and 22 controls. BBB permeability to water was measured with a new magnetic resonance imaging technique, water extraction with phase contrast arterial spin tagging. BBB permeability to albumin was determined using cerebrospinal fluid (CSF)/serum albumin ratio. Cognitive performance was assessed by domain-specific composite scores. AD pathology (including CSF Aβ and ptau) and vascular risk factors were examined. Compared to cognitively normal subjects, BBB in MCI patients manifested an increased permeability to small molecules such as water but was no more permeable to large molecules such as albumin. BBB permeability to water was found to be related to AD markers of CSF Aβ and ptau. On the other hand, BBB permeability to albumin was found to be related to vascular risk factors, especially hypercholesterolemia, but was not related to AD pathology. BBB permeability to small molecules, but not to large molecules, was found to be predictive of cognitive function. These findings provide early evidence that BBB breakdown is related to both AD and vascular risks, but their effects can be differentiated by spatial scales. BBB permeability to small molecules has a greater impact on cognitive performance. ANN NEUROL 2021;90:227-238.
Identifiants
pubmed: 34041783
doi: 10.1002/ana.26134
pmc: PMC8805295
mid: NIHMS1773734
doi:
Substances chimiques
ALB protein, human
0
Amyloid beta-Peptides
0
MAPT protein, human
0
Peptide Fragments
0
amyloid beta-protein (1-42)
0
tau Proteins
0
Serum Albumin, Human
ZIF514RVZR
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
227-238Subventions
Organisme : NINDS NIH HHS
ID : R01 NS106702
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG071515
Pays : United States
Organisme : NIH HHS
ID : R01 AG071515
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG064792
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB015909
Pays : United States
Organisme : NIH HHS
ID : S10 OD021648
Pays : United States
Organisme : NIH HHS
ID : R01 NS106711
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB031771
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066507
Pays : United States
Organisme : NIH HHS
ID : P41 EB015909
Pays : United States
Organisme : American Heart Association
ID : 19PRE34380371
Organisme : NINDS NIH HHS
ID : R01 NS106711
Pays : United States
Organisme : NIH HHS
ID : R01 AG064792
Pays : United States
Organisme : NIH HHS
ID : R01 NS106702
Pays : United States
Informations de copyright
© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
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