Undetectable gadolinium brain retention in individuals with an age‐dependent blood‐brain barrier breakdown in the hippocampus and mild cognitive impairment

Montagne, Axel; Huuskonen, Mikko T; Rajagopal, Gautham; Sweeney, Melanie D.; Nation, Daniel A.; Sepehrband, Farshid; D’Orazio, Lina M.; Harrington, Michael G.; Chui, Helena C.; Law, Meng; Toga, Arthur W.; Zloković, Berislav V.

doi:10.1016/j.jalz.2019.07.012

Cited by 23 publications

(19 citation statements)

References 52 publications

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“…In brief, we performed the analysis of the combined DCE datasets from both USC and WashU sites, and additionally site-specific analysis for each of the two sites separately, which showed no statistically significant differences across sites. Recently, we invited a subset of 52 participants for an additional T1-weighted scan without contrast (using the same scanner and same MR pulse sequences) after their first DCE-MRI 41 and measured both B 0 and T1 values at 2-year interval. This study showed that the results were unchanged and consistent across the scans, supporting minimal intra-site variability.…”

Section: Methodsmentioning

confidence: 99%

APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline

Montagne

Nation

Sagare

et al. 2020

Nature

Self Cite

835

793

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Section: Methodsmentioning

confidence: 99%

APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline

Montagne

Nation

Sagare

et al. 2020

Nature

Self Cite

835

793

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“…Furthermore, BBB collapse was demonstrated to be an early biomarker of human cognitive dysfunction beyond amyloid and tau ( 111 ). Moreover, preclinical investigation suggested that BBB disruption was antecedent to hippocampal atrophy in early AD patients; thus, the clinical view about BBB breakdown possibly occurring before neurodegeneration is proposed ( 112 ). Recently, aberrant BBB permeability changes to small molecules, such as water, could lead to clinical-detectable mild cognitive impairment (MCI) ( 113 ); of note, the emergence of MCI symptoms did not require BBB permeability larger enough to allow the penetrance of albumin ( 113 ).…”

Section: Chronic Inflammation Bbb Disruption and Nfandndmentioning

confidence: 99%

Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging

Mou¹,

Zhou

et al. 2022

Front. Immunol.

138

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It has been noticed in recent years that the unfavorable effects of the gut microbiota could exhaust host vigor and life, yet knowledge and theory are just beginning to be established. Increasing documentation suggests that the microbiota–gut–brain axis not only impacts brain cognition and psychiatric symptoms but also precipitates neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). How the blood–brain barrier (BBB), a machinery protecting the central nervous system (CNS) from the systemic circulation, allows the risky factors derived from the gut to be translocated into the brain seems paradoxical. For the unique anatomical, histological, and immunological properties underpinning its permeable dynamics, the BBB has been regarded as a biomarker associated with neural pathogenesis. The BBB permeability of mice and rats caused by GM dysbiosis raises the question of how the GM and its metabolites change BBB permeability and causes the brain pathophysiology of neuroinflammation and neurodegeneration (NF&ND) and brain aging, a pivotal multidisciplinary field tightly associated with immune and chronic systemic inflammation. If not all, gut microbiota-induced systemic chronic inflammation (GM-SCI) mainly refers to excessive gut inflammation caused by gut mucosal immunity dysregulation, which is often influenced by dietary components and age, is produced at the interface of the intestinal barrier (IB) or exacerbated after IB disruption, initiates various common chronic diseases along its dispersal routes, and eventually impairs BBB integrity to cause NF&ND and brain aging. To illustrate the immune roles of the BBB in pathophysiology affected by inflammatory or “leaky” IB resulting from GM and their metabolites, we reviewed the selected publications, including the role of the BBB as the immune barrier, systemic chronic inflammation and inflammation influences on BBB permeability, NF&ND, and brain aging. To add depth to the bridging role of systemic chronic inflammation, a plausible mechanism indispensable for BBB corruption was highlighted; namely, BBB maintenance cues are affected by inflammatory cytokines, which may help to understand how GM and its metabolites play a major role in NF&ND and aging.

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“…However, recent evidence indicates that subjects presenting early cognitive impairment had preexisting BBB damage. The platelet-derived growth factor receptor beta (PDGFRβ; Table 1 ) ( 243 , 244 ) shedding from perivascular pericytes was proposed as a biomarker of BBB integrity anticipating and predicting neurodegeneration ( 39 , 243 ). A high-sensitivity method for detecting pericyte injury quantifying PDGFRβ in CSF was recently proposed ( 245 ).…”

Section: Blood Biomarkers Of Nvu Damage: Available Analytical Tools mentioning

confidence: 99%

Peripheral Blood and Salivary Biomarkers of Blood–Brain Barrier Permeability and Neuronal Damage: Clinical and Applied Concepts

et al. 2021

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Within the neurovascular unit (NVU), the blood–brain barrier (BBB) operates as a key cerebrovascular interface, dynamically insulating the brain parenchyma from peripheral blood and compartments. Increased BBB permeability is clinically relevant for at least two reasons: it actively participates to the etiology of central nervous system (CNS) diseases, and it enables the diagnosis of neurological disorders based on the detection of CNS molecules in peripheral body fluids. In pathological conditions, a suite of glial, neuronal, and pericyte biomarkers can exit the brain reaching the peripheral blood and, after a process of filtration, may also appear in saliva or urine according to varying temporal trajectories. Here, we specifically examine the evidence in favor of or against the use of protein biomarkers of NVU damage and BBB permeability in traumatic head injury, including sport (sub)concussive impacts, seizure disorders, and neurodegenerative processes such as Alzheimer's disease. We further extend this analysis by focusing on the correlates of human extreme physiology applied to the NVU and its biomarkers. To this end, we report NVU changes after prolonged exercise, freediving, and gravitational stress, focusing on the presence of peripheral biomarkers in these conditions. The development of a biomarker toolkit will enable minimally invasive routines for the assessment of brain health in a broad spectrum of clinical, emergency, and sport settings.

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Undetectable gadolinium brain retention in individuals with an age‐dependent blood‐brain barrier breakdown in the hippocampus and mild cognitive impairment

Cited by 23 publications

References 52 publications

APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline

APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline

Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging

Peripheral Blood and Salivary Biomarkers of Blood–Brain Barrier Permeability and Neuronal Damage: Clinical and Applied Concepts

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