CR1 and the "Vanishing Amyloid" Hypothesis of Alzheimer's Disease.

Department of Psychiatry and Alzheimer's Disease Research Center
Biological psychiatry (Impact Factor: 9.47). 03/2013; 73(5):393-5. DOI: 10.1016/j.biopsych.2013.01.013
Source: PubMed


Available from: Sam Gandy, Sep 24, 2014
  • Source
    [Show abstract] [Hide abstract]
    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 in 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.
    Journal of Alzheimer's disease: JAD 06/2014; 42(3). DOI:10.3233/JAD-140144 · 3.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The complement component receptor 1 gene (CR1), which encodes a type-I transmembrane glycoprotein, has recently been identified as one of the most important risk genes for late-onset Alzheimer's disease (LOAD). In this article, we reviewed the recent evidence concerning the role of CR1 in LOAD. First, we introduced the structure, localization and physiological function of CR1 in humans. Afterward, we summarized the relation of CR1 polymorphisms with LOAD risk. Finally, we discussed the possible impact of CR1 on the pathogenesis of AD including amyloid-β pathology, tauopathy, immune dysfunction and glial-mediated neuroinflammation. We hope that a more comprehensive understanding of the role that CR1 played in AD may lead to the development of novel therapeutics for the prevention and treatment of AD.
    Molecular Neurobiology 05/2014; 51(2). DOI:10.1007/s12035-014-8723-8 · 5.29 Impact Factor
  • Source
    Letters in Drug Design &amp Discovery 01/2013; · 0.96 Impact Factor