Mostrar el registro sencillo del ítem
dc.contributor.author
Maarouf, Chera L.
dc.contributor.author
Daugs, Ian D.
dc.contributor.author
Spina, Salvatore
dc.contributor.author
Vidal, Ruben
dc.contributor.author
Kokjohn, Tyler A.
dc.contributor.author
Patton, R. Lyle
dc.contributor.author
Kalback, Walter M.
dc.contributor.author
Luehrs, Dean C.
dc.contributor.author
Walker, Douglas G.
dc.contributor.author
Castaño, Eduardo Miguel
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Beach, Thomas G.
dc.contributor.author
Ghetti, Bernardino
dc.contributor.author
Roher, Alex E.
dc.date.available
2017-07-21T19:38:42Z
dc.date.issued
2008-11
dc.identifier.citation
Maarouf, Chera L.; Daugs, Ian D.; Spina, Salvatore; Vidal, Ruben; Kokjohn, Tyler A.; et al.; Histopathological and molecular heterogeneity among individuals with dementia associated with Presenilin mutations; BioMed Central; Molecular Neurodegeneration; 3; 20; 11-2008; 1-18
dc.identifier.issn
1750-1326
dc.identifier.uri
http://hdl.handle.net/11336/21115
dc.description.abstract
BACKGROUND: Mutations in the presenilin (PSEN) genes are associated with early-onset familial Alzheimer's disease (FAD). Biochemical characterizations and comparisons have revealed that many PSEN mutations alter gamma-secretase activity to promote accumulation of toxic Abeta42 peptides. In this study, we compared the histopathologic and biochemical profiles of ten FAD cases expressing independent PSEN mutations and determined the degradation patterns of amyloid-beta precursor protein (AbetaPP), Notch, N-cadherin and Erb-B4 by gamma-secretase. In addition, the levels of Abeta40/42 peptides were quantified by ELISA. RESULTS: We observed a wide variation in type, number and distribution of amyloid deposits and neurofibrillary tangles. Four of the ten cases examined exhibited a substantial enrichment in the relative proportions of Abeta40 over Abeta42. The AbetaPP N-terminal and C-terminal fragments and Tau species, assessed by Western blots and scanning densitometry, also demonstrated a wide variation. The Notch-1 intracellular domain was negligible by Western blotting in seven PSEN cases. There was significant N-cadherin and Erb-B4 peptide heterogeneity among the different PSEN mutations. CONCLUSION: These observations imply that missense mutations in PSEN genes can alter a range of key gamma-secretase activities to produce an array of subtly different biochemical, neuropathological and clinical manifestations. Beyond the broad common features of dementia, plaques and tangles, the various PSEN mutations resulted in a wide heterogeneity and complexity and differed from sporadic AD.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
BioMed Central
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Presenilin
dc.subject
Fad
dc.subject
Mutations
dc.subject.classification
Bioquímica y Biología Molecular
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
Ciencias Biológicas
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.title
Histopathological and molecular heterogeneity among individuals with dementia associated with Presenilin mutations
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-07-18T14:50:26Z
dc.identifier.eissn
1750-1326
dc.journal.volume
3
dc.journal.number
20
dc.journal.pagination
1-18
dc.journal.pais
Reino Unido
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.journal.ciudad
London
dc.description.fil
Fil: Maarouf, Chera L.. Sun Health Research Institute; Estados Unidos
dc.description.fil
Fil: Daugs, Ian D.. Sun Health Research Institute; Estados Unidos
dc.description.fil
Fil: Spina, Salvatore. Universita Degli Studi Di Siena; Italia. Indiana University; Estados Unidos
dc.description.fil
Fil: Vidal, Ruben. Indiana University; Estados Unidos
dc.description.fil
Fil: Kokjohn, Tyler A.. Sun Health Research Institute; Estados Unidos. Midwestern University; Estados Unidos
dc.description.fil
Fil: Patton, R. Lyle. Sun Health Research Institute; Estados Unidos
dc.description.fil
Fil: Kalback, Walter M.. Sun Health Research Institute; Estados Unidos
dc.description.fil
Fil: Luehrs, Dean C.. Sun Health Research Institute; Estados Unidos
dc.description.fil
Fil: Walker, Douglas G.. Sun Health Research Institute; Estados Unidos
dc.description.fil
Fil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.description.fil
Fil: Beach, Thomas G.. Sun Health Research Institute; Estados Unidos
dc.description.fil
Fil: Ghetti, Bernardino. Indiana University; Estados Unidos
dc.description.fil
Fil: Roher, Alex E.. Sun Health Research Institute; Estados Unidos
dc.journal.title
Molecular Neurodegeneration
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/1750-1326-3-20
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1186/1750-1326-3-20
Archivos asociados