| 1. |
- Sweeney, M. D., et al.
(författare)
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Vascular dysfunction-The disregarded partner of Alzheimer's disease
- 2019
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:1, s. 158-167
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 2. |
- Gafson, A. R., et al.
(författare)
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Neurofilaments: neurobiological foundations for biomarker applications
- 2020
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 143:7, s. 1975-1998
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Tidskriftsartikel (refereegranskat)abstract
- Interest in neurofilaments has risen sharply in recent years with recognition of their potential as biomarkers of brain injury or neurodegeneration in CSF and blood. This is in the context of a growing appreciation for the complexity of the neurobiology of neurofilaments, new recognition of specialized roles for neurofilaments in synapses and a developing understanding of mechanisms responsible for their turnover. Here we will review the neurobiology of neurofilament proteins, describing current understanding of their structure and function, including recently discovered evidence for their roles in synapses. We will explore emerging understanding of the mechanisms of neurofilament degradation and clearance and review new methods for future elucidation of the kinetics of their turnover in humans. Primary roles of neurofilaments in the pathogenesis of human diseases will be described. With this background, we then will review critically evidence supporting use of neurofilament concentration measures as biomarkers of neuronal injury or degeneration. Finally, we will reflect on major challenges for studies of the neurobiology of intermediate filaments with specific attention to identifying what needs to be learned for more precise use and confident interpretation of neurofilament measures as biomarkers of neurodegeneration. © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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| 3. |
- Mehta, N. H., et al.
(författare)
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The Brain-Nose Interface: A Potential Cerebrospinal Fluid Clearance Site in Humans
- 2022
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The human brain functions at the center of a network of systems aimed at providing a structural and immunological layer of protection. The cerebrospinal fluid (CSF) maintains a physiological homeostasis that is of paramount importance to proper neurological activity. CSF is largely produced in the choroid plexus where it is continuous with the brain extracellular fluid and circulates through the ventricles. CSF movement through the central nervous system has been extensively explored. Across numerous animal species, the involvement of various drainage pathways in CSF, including arachnoid granulations, cranial nerves, perivascular pathways, and meningeal lymphatics, has been studied. Among these, there is a proposed CSF clearance route spanning the olfactory nerve and exiting the brain at the cribriform plate and entering lymphatics. While this pathway has been demonstrated in multiple animal species, evidence of a similar CSF egress mechanism involving the nasal cavity in humans remains poorly consolidated. This review will synthesize contemporary evidence surrounding CSF clearance at the nose-brain interface, examining across species this anatomical pathway, and its possible significance to human neurodegenerative disease. Our discussion of a bidirectional nasal pathway includes examination of the immune surveillance in the olfactory region protecting the brain. Overall, we expect that an expanded discussion of the brain-nose pathway and interactions with the environment will contribute to an improved understanding of neurodegenerative and infectious diseases, and potentially to novel prevention and treatment considerations. Copyright © 2022 Mehta, Sherbansky, Kamer, Carare, Butler, Rusinek, Chiang, Li, Strauss, Saint-Louis, Theise, Suss, Blennow, Kaplitt and de Leon.
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| 4. |
- Martikainen, Maria-Viola, et al.
(författare)
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TUBE project: Transport-derived ultrafines and the brain effects
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- The adverse effects of air pollutants on the respiratory and cardiovascular systems are unquestionable. However, in recent years, indications of effects beyond these organ systems have become more evident. Traffic-related air pollution has been linked with neurological diseases, exacerbated cognitive dysfunction, and Alzheimer’s disease. However, the exact air pollutant compositions and exposure scenarios leading to these adverse health effects are not known. Although several components of air pollution may be at play, recent experimental studies point to a key role of ultrafine particles (UFPs). While the importance of UFPs has been recognized, almost nothing is known about the smallest fraction of UFPs, and only >23 nm emissions are regulated in the EU. Moreover, the role of the semivolatile fraction of the emissions has been neglected. The Transport-Derived Ultrafines and the Brain Effects (TUBE) project will increase knowledge on harmful ultrafine air pollutants, as well as semivolatile compounds related to adverse health effects. By including all the major current combustion and emission control technologies, the TUBE project aims to provide new information on the adverse health effects of current traffic, as well as information for decision makers to develop more effective emission legislation. Most importantly, the TUBE project will include adverse health effects beyond the respiratory system; TUBE will assess how air pollution affects the brain and how air pollution particles might be removed from the brain. The purpose of this report is to describe the TUBE project, its background, and its goals.
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