Blood‐brain barrier breakdown, neuroinflammation, and cognitive decline in older adults

Bowman, Gene L.; Dayon, Loïc; Kirkland, Richard; Wojcik, Jérôme; Peyratout, Gwendoline; Severin, India C.; Henry, Hugues; Oikonomidi, Aikaterini; Migliavacca, Eugenia; Bacher, Michael; Popp, Julius

doi:10.1016/j.jalz.2018.06.2857

Cited by 229 publications

(180 citation statements)

References 74 publications

Supporting

Mentioning

170

Contrasting

Unclassified

Order By: Relevance

“…In conclusion, we report here that serotype b of the periodontopathogen Aa, associated with severe forms of PDis, caused specific inflammatory and immune responses in brain cells. These combined responses could increase the risk of AD, considering that a strong relationship between neuroinflammation and cognitive decline has been demonstrated recently [49]. Our results involve for the first time another important microbial agent in the etiology of the aggressive forms of PDis, the Aa, in the molecular mechanisms of AD pathogenesis.…”

Section: Discussionsupporting

confidence: 65%

Serotype b of Aggregatibacter actinomycetemcomitans triggers pro-inflammatory responses and amyloid beta secretion in hippocampal cells: a novel link between periodontitis and Alzheimer´s disease?

Díaz‐Zúñiga

Muñoz

Melgar‐Rodríguez

et al. 2019

Journal of Oral Microbiology

View full text Add to dashboard Cite

Introduction: Previous reports have proposed that Periodontal disease (PDis) predisposes to Alzheimer's disease (AD), both highly prevalent pathologies among the elderly. The bacteria Aggregatibacter actinomycetemcomitans (Aa), associated with the most aggressive forms of PDis, are classified in different serotypes with distinct virulence according to the antigenicity of their lipopolysaccharide (LPS). Methods: Here, we determined the effects of purified LPS, from serotypes a, b or c of Aa, on primary cultures of microglia or mixed hippocampal cells. Results: We found that both culture types exhibited higher levels of inflammatory cytokines (IL-1β, IL-6 and TNFα) when treated with serotype b-LPS, compared with controls, as quantified by qPCR and/or ELISA. Also, cultures treated with serotype a-LPS displayed increased mRNA levels of the modulatory cytokines IL-4 and IL-10. Mixed hippocampal cultures treated with serotype b-LPS exhibited severe neuronal morphological changes and displayed increased levels of secreted Aβ 1-42 peptide. These results indicate that LPS from different Aa serotypes triggers discriminatory immune responses, which differentially affect primary hippocampal cells. Conclusion: Altogether, our results show that treatment with serotype b-LPS triggers the secretion of proinflammatory cytokines by microglia, induces neurite shrinking, and increases the extracellular Aβ1-42 levels, all features strongly associated with the etiology of AD.

show abstract

Section: Discussionsupporting

confidence: 65%

Serotype b of Aggregatibacter actinomycetemcomitans triggers pro-inflammatory responses and amyloid beta secretion in hippocampal cells: a novel link between periodontitis and Alzheimer´s disease?

Díaz‐Zúñiga

Muñoz

Melgar‐Rodríguez

et al. 2019

Journal of Oral Microbiology

View full text Add to dashboard Cite

show abstract

“…Findings from dynamic contrast arterial imaging that depicts increased hippocampal BBB permeability in MCI compared to age‐matched NC controls offer strong evidence that BBB integrity is compromised in MCI [22]. Moreover, recent findings from Bowman and colleagues [23] showed an association between increased BBB permeability measured by serum/CSF albumin ratio and worse cognitive decline in older adults with MCI. However, to date, no direct comparison of BBB permeability with plasma NFL concentrations or the slope of the correlation of plasma NFL with CSF NFL in the context of neurodegeneration has been reported to examine this hypothesis closer, though a small pilot study suggests blood NFL concentration is unaffected by BBB permeability [24].…”

Section: Discussionmentioning

confidence: 94%

Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition

Osborn

Khan

Kresge

et al. 2019

Alz & Dem Diag Ass & Dis Mo

View full text Add to dashboard Cite

Introduction Neuroaxonal damage may contribute to cognitive changes preceding clinical dementia. Accessible biomarkers are critical for detecting such damage. Methods Plasma and cerebrospinal fluid (CSF) neurofilament light (NFL) were related to neuropsychological performance among Vanderbilt Memory & Aging Project participants (plasma n = 333, 73 ± 7 years; CSF n = 149, 72 ± 6 years) ranging from normal cognition (NC) to mild cognitive impairment (MCI). Models adjusted for age, sex, race/ethnicity, education, apolipoprotein E ε4 carriership, and Framingham Stroke Risk Profile. Results Plasma NFL was related to all domains (P values ≤ .008) except processing speed (P values ≥ .09). CSF NFL was related to memory and language (P values ≤ .04). Interactions with cognitive diagnosis revealed widespread plasma associations, particularly in MCI participants, which were further supported in head‐to‐head comparison models. Discussion Plasma and CSF NFL (reflecting neuroaxonal injury) relate to cognition among non‐demented older adults albeit with small to medium effects. Plasma NFL shows particular promise as an accessible biomarker with relevance to cognition in MCI.

show abstract

“…Vascular inflammation results from aging [199,200] and can be enforced by metabolic and cardiovascular diseases [201,202]. An important mediator of vascular inflammation is thrombin, which can directly activate endothelial cells and enhance the expression of pro-inflammatory proteins such as ICAM-1 and MCP-1, angiopoietin-2 release and the up-regulation of αVβ3 integrin [189].…”

Section: Vascular Inflammationmentioning

confidence: 99%

An Integrated View on Vascular Dysfunction in Alzheimer’s Disease

Klohs

2019

Neurodegener Dis

View full text Add to dashboard Cite

Background: Cerebrovascular disease is a common comorbidity in patients with Alzheimer's disease (AD). It is believed to contribute additively to the cognitive impairment and to lower the threshold for the development of dementia. However, accumulating evidence suggests that dysfunction of the cerebral vasculature and AD neuropathology interact in multiple ways. Vascular processes even proceed AD neuropathology, implicating a causal role in the etiology of AD. Thus, the review aims to provide an integrated view on vascular dysfunction in AD. Summary: In AD, the cerebral vasculature undergoes pronounced cellular, morphological and structural changes, which alters regulation of blood flow, vascular fluid dynamics and vessel integrity. Stiffening of central blood vessels lead to transmission of excessive pulsatile energy to the brain microvasculature, causing endorgan damage. Moreover, a dysregulated hemostasis and chronic vascular inflammation further impede vascular function, where its mediators interact synergistically. Changes of the cerebral vasculature are triggered and driven by systemic vascular abnormalities that are part of aging, and which can be accelerated and aggravated by cardiovascular diseas-es. Key Messages: In AD, the cerebral vasculature is the locus where multiple pathogenic processes converge and contribute to cognitive impairment. Understanding the molecular mechanism and pathophysiology of vascular dysfunction in AD and use of vascular blood-based and imaging biomarker in clinical studies may hold promise for future prevention and therapy of the disease.

show abstract

Blood‐brain barrier breakdown, neuroinflammation, and cognitive decline in older adults

Cited by 229 publications

References 74 publications

Serotype b of Aggregatibacter actinomycetemcomitans triggers pro-inflammatory responses and amyloid beta secretion in hippocampal cells: a novel link between periodontitis and Alzheimer´s disease?

Serotype b of Aggregatibacter actinomycetemcomitans triggers pro-inflammatory responses and amyloid beta secretion in hippocampal cells: a novel link between periodontitis and Alzheimer´s disease?

Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition

An Integrated View on Vascular Dysfunction in Alzheimer’s Disease

Contact Info

Product

Resources

About