Linked Life Data

20726888

Source:http://linkedlifedata.com/resource/pubmed/id/20726888

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2010-11-2
pubmed:abstractText
Alzheimer's disease (AD) is the most common dementia-causing disorder in the elderly; it may be related to multiple risk factors, and is characterized pathologically by cerebral hypometabolism, paravascular ?-amyloid peptide (A?) plaques, neuritic dystrophy, and intra-neuronal aggregation of phosphorylated tau. To explore potential pathogenic links among some of these lesions, we examined ?-secretase-1 (BACE1) alterations relative to A? deposition, neuritic pathology and vascular organization in aged monkey and AD human cerebral cortex. Western blot analyses detected increased levels of BACE1 protein and ?-site-cleavage amyloid precursor protein C-terminal fragments in plaque-bearing human and monkey cortex relative to controls. In immunohistochemistry, locally elevated BACE1 immunoreactivity (IR) occurred in AD but not in control human cortex, with a trend for increased overall density among cases with greater plaque pathology. In double-labeling preparations, BACE1 IR colocalized with immunolabeling for A? but not for phosphorylated tau. In perfusion-fixed monkey cortex, locally increased BACE1 IR co-existed with intra-axonal and extracellular A? IR among virtually all neuritic plaques, ranging from primitive to typical cored forms. This BACE1 labeling localized to swollen/sprouting axon terminals that might co-express one or another neuronal phenotype markers (GABAergic, glutamatergic, cholinergic, or catecholaminergic). Importantly, these BACE1-labeled dystrophic axons resided near to or in direct contact with blood vessels. These findings suggest that plaque formation in AD or normal aged primates relates to a multisystem axonal pathogenesis that occurs in partnership with a potential vascular or metabolic deficit. The data provide a mechanistic explanation for why senile plaques are present preferentially near the cerebral vasculature.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1460-9568
pubmed:author
pubmed:copyrightInfo
© 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
pubmed:issnType
Electronic
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1223-38
pubmed:dateRevised
2011-10-3
pubmed:meshHeading
pubmed-meshheading:20726888-Aging, pubmed-meshheading:20726888-Alzheimer Disease, pubmed-meshheading:20726888-Amyloid Precursor Protein Secretases, pubmed-meshheading:20726888-Amyloid beta-Peptides, pubmed-meshheading:20726888-Animals, pubmed-meshheading:20726888-Aspartic Acid Endopeptidases, pubmed-meshheading:20726888-Blood Vessels, pubmed-meshheading:20726888-Cerebral Cortex, pubmed-meshheading:20726888-Electron Transport Complex IV, pubmed-meshheading:20726888-Female, pubmed-meshheading:20726888-Gene Expression Regulation, pubmed-meshheading:20726888-Humans, pubmed-meshheading:20726888-Macaca mulatta, pubmed-meshheading:20726888-Male, pubmed-meshheading:20726888-Molecular Weight, pubmed-meshheading:20726888-NADPH Dehydrogenase, pubmed-meshheading:20726888-Nerve Tissue Proteins, pubmed-meshheading:20726888-Plaque, Amyloid, pubmed-meshheading:20726888-Postmortem Changes, pubmed-meshheading:20726888-Presynaptic Terminals, pubmed-meshheading:20726888-Silver Staining, pubmed-meshheading:20726888-Statistics, Nonparametric, pubmed-meshheading:20726888-tau Proteins
pubmed:year
2010
pubmed:articleTitle
?-Secretase-1 elevation in aged monkey and Alzheimer's disease human cerebral cortex occurs around the vasculature in partnership with multisystem axon terminal pathogenesis and ?-amyloid accumulation.
pubmed:affiliation
Department of Anatomy and Neurobiology, Central South University Xiangya Medical School, Changsha, Hunan, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural