Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It?
| Autor: | Laura G McNamara, Richard L.M. Faull, Karan Govindpani, Chitra Vinnakota, Andrea Kwakowsky, Nicholas R Smith, Henry J Waldvogel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Apolipoprotein E
Amyloid Angiogenesis lcsh:Medicine Disease Review Blood–brain barrier medicine.disease_cause Bioinformatics 03 medical and health sciences 0302 clinical medicine medicine Dementia neurovascular unit 030304 developmental biology 0303 health sciences business.industry β-amyloid lcsh:R Neurotoxicity General Medicine vascular dysfunction blood-brain barrier medicine.disease medicine.anatomical_structure business Alzheimer’s disease 030217 neurology & neurosurgery Oxidative stress APOE |
| Zdroj: | Journal of Clinical Medicine, Vol 8, Iss 5, p 651 (2019) Journal of Clinical Medicine |
| ISSN: | 2077-0383 |
| Popis: | Alzheimer’s disease (AD) is the most prevalent form of dementia. Despite decades of research following several theoretical and clinical lines, all existing treatments for the disorder are purely symptomatic. AD research has traditionally been focused on neuronal and glial dysfunction. Although there is a wealth of evidence pointing to a significant vascular component in the disease, this angle has been relatively poorly explored. In this review, we consider the various aspects of vascular dysfunction in AD, which has a significant impact on brain metabolism and homeostasis and the clearance of β-amyloid and other toxic metabolites. This may potentially precede the onset of the hallmark pathophysiological and cognitive symptoms of the disease. Pathological changes in vessel haemodynamics, angiogenesis, vascular cell function, vascular coverage, blood-brain barrier permeability and immune cell migration may be related to amyloid toxicity, oxidative stress and apolipoprotein E (APOE) genotype. These vascular deficits may in turn contribute to parenchymal amyloid deposition, neurotoxicity, glial activation and metabolic dysfunction in multiple cell types. A vicious feedback cycle ensues, with progressively worsening neuronal and vascular pathology through the course of the disease. Thus, a better appreciation for the importance of vascular dysfunction in AD may open new avenues for research and therapy. |
| Databáze: | OpenAIRE |
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