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Expression of APP p...
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Matsui, Toshifumi
(author)
Expression of APP pathway mRNAs and proteins in Alzheimer's disease
- Article/chapterEnglish2007
Publisher, publication year, extent ...
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Elsevier BV,2007
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-144030
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-144030URI
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https://doi.org/10.1016/j.brainres.2007.05.050DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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In both trisomy 21 and rare cases of triplication of amyloid precursor protein (APP) Alzheimer's disease (AD) pathological changes are believed to be secondary to increased expression of APP. We hypothesized that sporadic AD may also be associated with changes in transcription of APP or its metabolic partners. To address this issue, temporal neocortex of 27 AD and 21 non-demented control brains was examined to assess mRNA levels of APP isoforms (total APP, APP containing the Kunitz protease inhibitor domain [APP-KPI] and APP770) and APP metabolic enzymatic partners (the APP cleaving enzymes beta-secretase [BACE] and presenilin-1 [PS- 1], and putative clearance molecules, low-density lipoprotein receptor protein [LRP] and apolipoprotein E [apoE]). Furthermore, we evaluated how changes in APP at the mRNA level affect the amount of Tris buffer extractable APP protein and A beta 40 and 42 peptides in AD and control brains. As assessed by quantitative PCR, APP-KPI (p=0.007), APP770 (p=0.004), PS-1 (p = 0.004), LRP (p = 0.003), apoE (p = 0.0002) and GFAP (p < 0.0001) mRNA levels all increased in AD, and there was a shift from APP695 (a neuronal isoform) towards KPI containing isoforms that are present in glia as well. APP-KPI mRNA levels correlated with soluble APP alpha -KPI protein (sAPP alpha -KPI) levels measured by ELISA (T= 0.33, p = 0.015 by Kendall's rank correlation); in turn, soluble APP alpha-KPI protein levels positively correlated with Tris -extractable, soluble A beta 40 (p=0.046) and 42 levels (p=0.007). The ratio of soluble APP alpha-KPI protein levels to total APP protein increased in AD, and also correlated with GFAP protein levels in AD. These results suggest that altered transcription of APP in AD is proportionately associated with A beta peptide, may occur in the context of gliosis, and may contribute to A beta deposition in sporadic AD.
Subject headings and genre
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Alzheimer's disease
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APP
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A beta
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Kunitz
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microglia
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MEDICINE
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MEDICIN
Added entries (persons, corporate bodies, meetings, titles ...)
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Ingelsson, MartinUppsala universitet,Institutionen för folkhälso- och vårdvetenskap(Swepub:uu)maing121
(author)
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Fukumoto, Hiroaki
(author)
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Ramasamy, Karunya
(author)
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Kowa, Hisatomo
(author)
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Frosch, Matthew P.
(author)
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Irizarry, Michael C.
(author)
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Hyman, Bradley T.
(author)
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Uppsala universitetInstitutionen för folkhälso- och vårdvetenskap
(creator_code:org_t)
Related titles
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In:Brain Research: Elsevier BV1161, s. 116-1230006-89931872-6240
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