Linked Life Data

12486146

Source:http://linkedlifedata.com/resource/pubmed/id/12486146

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2002-12-17
pubmed:abstractText
The most frequent human apolipoprotein (apo) E isoforms, E3 and E4, differentially affect Alzheimer's disease (AD) risk (E4 > E3) and age of onset (E4 < E3). Compared with apoE3, apoE4 promotes the cerebral deposition of amyloid beta (Abeta) peptides, which are derived from the amyloid precursor protein (APP) and play a central role in AD. However, it is uncertain whether Abeta deposition into plaques is the main mechanism by which apoE isoforms affect AD. We analyzed murine apoE-deficient transgenic mice expressing in their brains human APP (hAPP) and Abeta together with apoE3 or apoE4. Because cognitive decline in AD correlates better with decreases in synaptophysin-immunoreactive presynaptic terminals, choline acetyltransferase (ChAT) activity, and ChAT-positive fibers than with plaque load, we compared these parameters in hAPP/apoE3 and hAPP/apoE4 mice and singly transgenic controls at 6-7, 12-15, and 19-24 months of age. Brain aging in the context of high levels of nondeposited human Abeta resulted in progressive synaptic/cholinergic deficits. ApoE3 delayed the synaptic deficits until old age, whereas apoE4 was not protective at any of the ages analyzed. Old hAPP/apoE4 mice had more plaques than old hAPP/apoE3 mice, but synaptic/cholinergic deficits preceded plaque formation in hAPP/apoE4 mice. Moreover, despite their different plaque loads, old hAPP/apoE4 and hAPP/apoE3 mice had comparable synaptic/cholinergic deficits, and these deficits were found not only in the hippocampus but also in the neocortex, which in most mice contained no plaques. Thus, apoE3, but not apoE4, delays age- and Abeta-dependent synaptic deficits through a plaque-independent mechanism. This difference could contribute to the differential effects of apoE isoforms on the risk and onset of AD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10539-48
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12486146-Age Factors, pubmed-meshheading:12486146-Alzheimer Disease, pubmed-meshheading:12486146-Amyloid beta-Peptides, pubmed-meshheading:12486146-Amyloid beta-Protein Precursor, pubmed-meshheading:12486146-Animals, pubmed-meshheading:12486146-Apolipoprotein E3, pubmed-meshheading:12486146-Apolipoprotein E4, pubmed-meshheading:12486146-Apolipoproteins E, pubmed-meshheading:12486146-Brain, pubmed-meshheading:12486146-Choline O-Acetyltransferase, pubmed-meshheading:12486146-Cholinergic Fibers, pubmed-meshheading:12486146-Humans, pubmed-meshheading:12486146-Immunohistochemistry, pubmed-meshheading:12486146-Mice, pubmed-meshheading:12486146-Mice, Transgenic, pubmed-meshheading:12486146-Peptide Fragments, pubmed-meshheading:12486146-Presynaptic Terminals, pubmed-meshheading:12486146-Protein Isoforms, pubmed-meshheading:12486146-Synaptophysin
pubmed:year
2002
pubmed:articleTitle
Modulation of Alzheimer-like synaptic and cholinergic deficits in transgenic mice by human apolipoprotein E depends on isoform, aging, and overexpression of amyloid beta peptides but not on plaque formation.
pubmed:affiliation
Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94141-9100, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't