title: The effects of impaired cerebral circulation on Alzheimer's disease pathology: evidence from animal studies.
abstract: Persistent systemic hypoxia, a direct consequence of alterations in vascular function, can compromise the brain by increasing the risk of developing dementias such as Alzheimer's disease (AD). Vascular contributions to cognitive impairment and AD in aged individuals are common, and several vascular risk factors for AD are linked to hypoxia. Clinical evidence confirms that structural and functional changes characteristic of AD pathology also occur following hypoxic-ischemic events such as stroke and traumatic brain injury. Studies with transgenic and non-transgenic mouse models reliably show that hypoxia increases the levels of amyloid-β peptides that form the characteristic plaques in AD brains. Moreover, some studies suggest that vascular lesions also promote tau phosphorylation, modulate apolipoprotein E expression, and have more profound effects in aged animals, but additional evidence is needed to establish these findings. Although the mechanisms underlying hypoxia-related effects remain unclear, controlled animal studies continue to reveal mechanistic aspects of the relationship between hypoxia and AD pathology that are necessary for therapeutic developments. The present review summarizes evidence from rodent studies regarding the effects of hypoxia on AD-related pathology and evaluates its impact on understanding human disease.
authors.affiliation: Center for Neuroscience, INDICASAT AIP, City of Knowledge, Republic of Panama Department of Biotechnology, Acharya Nagarjuna University, Guntur, India.
authors.forename: Alcibiades E
authors.initials: AE
authors.lastname: Villarreal
authors.affiliation: Department of Psychology and Program in Neuroscience, Lafayette College, Easton, PA, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Barron
authors.affiliation: Center for Neuroscience, INDICASAT AIP, City of Knowledge, Republic of Panama.
authors.forename: K S
authors.initials: KS
authors.lastname: Rao
authors.affiliation: Center for Neuroscience, INDICASAT AIP, City of Knowledge, Republic of Panama.
authors.forename: Gabrielle B
authors.initials: GB
authors.lastname: Britton
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000473:pathology*; D000818:Animals; D002545:Brain Ischemia / Q000150:complications*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans
keywords: Amyloid-β; apolipoprotein E; cerebral amyloid angiopathy; cerebral hypoxia; ischemia; tau protein