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http://hdl.handle.net/1942/30271
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DC Field | Value | Language |
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dc.contributor.author | DEWACHTER, Ilse | - |
dc.contributor.author | Reversé, Delphine | - |
dc.contributor.author | Caluwaerts, Nathalie | - |
dc.contributor.author | Ris, Laurence | - |
dc.contributor.author | Kuipéri, Cuno | - |
dc.contributor.author | Van den Haute, Chris | - |
dc.contributor.author | Spittaels, Kurt | - |
dc.contributor.author | Umans, Lieve | - |
dc.contributor.author | Serneels, Lutgarde | - |
dc.contributor.author | Thiry, Els | - |
dc.contributor.author | Moechars, Dieder | - |
dc.contributor.author | Mercken, Mark | - |
dc.contributor.author | Godaux, Emile | - |
dc.contributor.author | Van Leuven, Fred | - |
dc.date.accessioned | 2020-01-09T15:00:27Z | - |
dc.date.available | 2020-01-09T15:00:27Z | - |
dc.date.issued | 2002 | - |
dc.date.submitted | 2020-01-09T12:29:34Z | - |
dc.identifier.issn | 0270-6474 | - |
dc.identifier.uri | http://hdl.handle.net/1942/30271 | - |
dc.description.abstract | In the brain of Alzheimer's disease (AD) patients, neurotoxic amyloid peptides accumulate and are deposited as senile plaques. A major therapeutic strategy aims to decrease production of amyloid peptides by inhibition of gamma-secretase. Presenilins are polytopic transmembrane proteins that are essential for gamma-secretase activity during development and in amyloid production. By loxP/Cre-recombinase-mediated deletion, we generated mice with postnatal, neuron-specific presenilin-1 (PS1) deficiency, denoted PS1(n-/-), that were viable and fertile, with normal brain morphology. In adult PS1(n-/-) mice, levels of endogenous brain amyloid peptides were strongly decreased, concomitant with accumulation of amyloid precursor protein (APP) C-terminal fragments. In the cross of APP[V717I]xPS1 (n-/-) double transgenic mice, the neuronal absence of PS1 effectively prevented amyloid pathology, even in mice that were 18 months old. This contrasted sharply with APP[V717I] single transgenic mice that all develop amyloid pathology at the age of 10-12 months. In APP[V717I]xPS1 (n-/-) mice, long-term potentiation (LTP) was practically rescued at the end of the 2 hr observation period, again contrasting sharply with the strongly impaired LTP in APP[V717I] mice. The findings demonstrate the critical involvement of amyloid peptides in defective LTP in APP transgenic mice. Although these data open perspectives for therapy of AD by gamma-secretase inhibition, the neuronal absence of PS1 failed to rescue the cognitive defect, assessed by the object recognition test, of the parent APP[V717I] transgenic mice. This points to potentially detrimental effects of accumulating APP C99 fragments and demands further study of the consequences of inhibition of gamma-secretase activity. In addition, our data highlight the complex functional relation of APP and PS1 to cognition and neuronal plasticity in adult and aging brain. | - |
dc.language.iso | en | - |
dc.publisher | SOC NEUROSCIENCE | - |
dc.rights | 2002 Society for Neuroscience | - |
dc.subject.other | PS1 | - |
dc.subject.other | Alzheimer’s disease | - |
dc.subject.other | neuronal plasticity | - |
dc.subject.other | cognition | - |
dc.subject.other | amyloid pathology | - |
dc.subject.other | mouse model | - |
dc.title | Neuronal deficiency of presenilin 1 inhibits amyloid plaque formation and corrects hippocampal long-term potentiation but not a cognitive defect of amyloid precursor protein [V717I] transgenic mice | - |
dc.type | Research Report | - |
dc.identifier.epage | 3453 | - |
dc.identifier.issue | 9 | - |
dc.identifier.spage | 3445-53 | - |
dc.identifier.volume | 22 | - |
local.bibliographicCitation.jcat | A1 | - |
local.publisher.place | 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA | - |
local.type.refereed | Refereed | - |
local.type.specified | Research Report | - |
dc.source.type | Article | - |
dc.identifier.pmid | 11978821 | - |
dc.identifier.isi | 000175296200022 | - |
dc.identifier.eissn | 1529-2401 | - |
local.provider.type | PubMed | - |
local.uhasselt.uhpub | no | - |
item.fullcitation | DEWACHTER, Ilse; Reversé, Delphine; Caluwaerts, Nathalie; Ris, Laurence; Kuipéri, Cuno; Van den Haute, Chris; Spittaels, Kurt; Umans, Lieve; Serneels, Lutgarde; Thiry, Els; Moechars, Dieder; Mercken, Mark; Godaux, Emile & Van Leuven, Fred (2002) Neuronal deficiency of presenilin 1 inhibits amyloid plaque formation and corrects hippocampal long-term potentiation but not a cognitive defect of amyloid precursor protein [V717I] transgenic mice. | - |
item.fulltext | With Fulltext | - |
item.accessRights | Open Access | - |
item.contributor | DEWACHTER, Ilse | - |
item.contributor | Reversé, Delphine | - |
item.contributor | Caluwaerts, Nathalie | - |
item.contributor | Ris, Laurence | - |
item.contributor | Kuipéri, Cuno | - |
item.contributor | Van den Haute, Chris | - |
item.contributor | Spittaels, Kurt | - |
item.contributor | Umans, Lieve | - |
item.contributor | Serneels, Lutgarde | - |
item.contributor | Thiry, Els | - |
item.contributor | Moechars, Dieder | - |
item.contributor | Mercken, Mark | - |
item.contributor | Godaux, Emile | - |
item.contributor | Van Leuven, Fred | - |
crisitem.journal.issn | 0270-6474 | - |
crisitem.journal.eissn | 1529-2401 | - |
Appears in Collections: | Research publications |
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File | Description | Size | Format | |
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3445.full.pdf | 461.66 kB | Adobe PDF | View/Open |
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