Article

Dementia from Alzheimer disease and mixed pathologies in the oldest old.

Rush University Medical Center, Chicago, Illinois, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 29.98). 05/2012; 307(17):1798-800. DOI: 10.1001/jama.2012.3556
Source: PubMed
0 Bookmarks
 · 
98 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer's disease (AD) is a common neurodegenerative disease in elderly individuals, and effective therapies are unavailable. This study was designed to investigate the neuroprotective effects of sulforaphane (an activator of NF-E2-related factor 2) on mice with AD-like lesions induced by combined administration of aluminum and d-galactose. Step-down-type passive avoidance tests showed sulforaphane ameliorated cognitive impairment in AD-like mice. Immunohistochemistry results indicated sulforaphane attenuated cholinergic neuron loss in the medial septal and hippocampal CA1 regions in AD-like mice. However, spectrophotometry revealed no significant difference in acetylcholine level or the activity of choline acetyltransferase or acetylcholinesterase in the cerebral cortex among groups of control and AD-like mice with and without sulforaphane treatment. Sulforaphane significantly increased the numbers of 5-bromo-2'-deoxyuridine-positive neurons in the subventricular and subgranular zones in AD-like mice which were significantly augmented compared with controls. Atomic absorption spectrometry revealed significantly lower aluminum levels in the brains of sulforaphane-treated AD-like mice than in those that did not receive sulforaphane treatment. In conclusion, sulforaphane ameliorates neurobehavioral deficits by reducing cholinergic neuron loss in the brains of AD-like mice, and the mechanism may be associated with neurogenesis and aluminum load reduction. These findings suggest that phytochemical sulforaphane has potential application in AD therapeutics.
    International Journal of Molecular Sciences 01/2014; 15(8):14396-410. · 2.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Scientific evidence continues to demonstrate the linkage of vascular contributions to cognitive impairment and dementia such as Alzheimer's disease. In December, 2013, the Alzheimer's Association, with scientific input from the National Institute of Neurological Disorders and Stroke and the National Heart, Lung and Blood Institute from the National Institutes of Health, convened scientific experts to discuss the research gaps in our understanding of how vascular factors contribute to Alzheimer's disease and related dementia. This manuscript summarizes the meeting and the resultant discussion, including an outline of next steps needed to move this area of research forward. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 12/2014; · 14.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The increasing prevalence of Alzheimer's disease (AD) and a lack of effective prevention or disease-modifying therapies are global challenges with devastating personal, social and economic consequences. The amyloid β (Aβ) hypothesis posits that cerebral β-amyloidosis is a critical early event in AD pathogenesis. However, failed clinical trials of Aβ-centric drug candidates have called this hypothesis into question. Whereas we acknowledge that the Aβ hypothesis is far from disproven, we here re-visit the links between Aβ, tau and neurodegeneration. We review the genetics, epidemiology and pathology of sporadic AD and give an updated account of what is currently known about the molecular pathogenesis of the disease.
    Expert Review of Neurotherapeutics 06/2014; 14(6):621-30. · 2.96 Impact Factor

Full-text (2 Sources)

Download
21 Downloads
Available from
May 23, 2014