Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-4-10
pubmed:abstractText
Aggregation of amyloid-beta (Abeta) peptide into soluble and insoluble forms within the brain extracellular space is central to the pathogenesis of Alzheimer's disease. Full-length amyloid precursor protein (APP) is endocytosed from the cell surface into endosomes where it is cleaved to produce Abeta. Abeta is subsequently released into the brain interstitial fluid (ISF). We hypothesized that synaptic transmission results in more APP endocytosis, thereby increasing Abeta generation and release into the ISF. We found that inhibition of clathrin-mediated endocytosis immediately lowers ISF Abeta levels in vivo. Two distinct methods that increased synaptic transmission resulted in an elevation of ISF Abeta levels. Inhibition of endocytosis, however, prevented the activity-dependent increase in Abeta. We estimate that approximately 70% of ISF Abeta arises from endocytosis-associated mechanisms, with the vast majority of this pool also dependent on synaptic activity. These findings have implications for AD pathogenesis and may provide insights into therapeutic intervention.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-10531052, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-10623648, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-10924255, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-11117548, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-11274343, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-11604140, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-12427834, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-12427835, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-12598899, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-12670422, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-12686572, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-1325974, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-14523085, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-14663028, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-15126508, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-15294142, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-15668449, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-15705569, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-16095541, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-16120771, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-16174740, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-16221845, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-16364896, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-16452683, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-16469784, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-16504943, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-16957580, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-17065436, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-17093049, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-17145504, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-17151169, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-17185415, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-17220890, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-17360908, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-17463283, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-17551018, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-4348786, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-7407615, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-8021238, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-8059603, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-8245121, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-8416966, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-8446635, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-8621605, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-8743946, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-8810256, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-8943215, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-8987743, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-9066363, http://linkedlifedata.com/resource/pubmed/commentcorrection/18400162-9651678
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1097-4199
pubmed:author
pubmed:issnType
Electronic
pubmed:day
10
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
42-51
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
More...