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| Content Provider | Springer Nature Link |
|---|---|
| Author | Daulatzai, Mak Adam |
| Copyright Year | 2012 |
| Abstract | Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. The human brain is extremely sensitive to hypoxia, ischemia, and glucose depletion. Impaired delivery of oxygen in obstructive sleep apnea (OSA) alters neuronal homeostasis, induces pathology, and triggers neuronal degeneration/death. This article systematically delineates the steps in the complex cascade leading to AD, focusing on pathology caused by chronic intermittent hypoxia, hypertension, brain hypoperfusion, glucose dysmetabolism, and endothelial dysfunction. Hypoxia/hypoxemia underpins several pathological processes including sympathetic activation, chemoreflex activity, neuroinflammation, oxidative stress, and a host of perturbations leading to neurodegeneration. The arterial blood flow reduction in OSA is profound, being about 76 % in obstructive hypopneas and 80 % in obstructive apneas; this leads to cerebral ischemia promoting neuronal apoptosis in neocortex and brainstem. OSA pathology also includes gray matter loss in the frontal, parietal, temporal, and occipital cortices, the thalamus, hippocampus, and key brainstem nuclei including the nucleus tractus solitarius. (18)F-FDG PET studies on OSA and AD patients, and animal models of AD, have shown reduced cerebral glucose metabolism in the above mentioned brain regions. Owing to the pathological impact of hypoxia, hypertension, hypoperfusion and impaired glucose metabolism, the adverse cardiovascular, neurocirculatory and metabolic consequences upregulate amyloid beta generation and tau phosphorylation, and lead to memory/cognitive impairment—culminating in AD. The framework encompassing these factors provides a pragmatic neuropathological approach to explain onset of Alzheimer’s dementia. The basic tenets of the current paradigm should influence the design of therapeutic strategies to ameliorate AD. |
| Starting Page | 2627 |
| Ending Page | 2658 |
| Page Count | 32 |
| File Format | |
| ISSN | 03643190 |
| Journal | Neurochemical Research |
| Volume Number | 37 |
| Issue Number | 12 |
| e-ISSN | 15736903 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2012-08-12 |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Alzheimer’s disease Amyloid-β Obstructive sleep apnea Hypoxia Hypoxemia Hypertension Neuroinflammation Cerebral hypoperfusion Nucleus of the solitary tract Neurosciences Neurochemistry Biochemistry Cell Biology Neurology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Biochemistry Cellular and Molecular Neuroscience |
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