What are the links between hypoxia and Alzheimer’s disease?

Abstract

Rahul Lall,1 Raihan Mohammed,1 Utkarsh Ojha21Department of Medicine, University of Cambridge, Cambridge, UK; 2Faculty of Medicine, Imperial College London, London, UKAbstract: Alzheimer’s disease (AD) is the most common neurodegenerative disease. Histological characterization of amyloid plaques and neurofibrillary tangles in the brains of AD patients, alongside genetic studies in individuals suffering the familial form of the disease, has fueled the accumulation of the amyloid-β protein as the initial pathological trigger of disease. Association studies have recently showed that cerebral hypoxia, via both genetic and epigenetic mechanisms, increase amyloid-β deposition by altering expression levels of enzymes involved in the production/degradation of the protein. Furthermore, hypoxia has also been linked to neuronal and glial-cell calcium dysregulation through formation of calcium-permeable pores, dysregulated glutamate signaling, and intracellular calcium-store dysfunction. Hypoxia has also been strongly linked to neuroinflammation; however, this relationship to AD has not been thoroughly discussed in the literature. Here, we highlight and organize critical research evidence showing that in both hypoxic and AD brains, there are similarities in terms of 1) the substances mediating/modulating the neuroinflammatory environment and 2) the immune cells that drive the formation of these substances.Keywords: hypoxia, AB accumulation, amyloid, calcium, neuroinflammation, ischemia

Keywords

• Hypoxia
• AB accumulation
• amyloid
• calcium
• neuroinflammation
• microglia
• ischaemia