liu.seSearch for publications in DiVA
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Increased expression of the lysosomal cholesterol transporter NPC1 in Alzheimers disease
Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Hälsouniversitetet.
Prince of Wales Medical Research Institute.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
Prince of Wales Medical Research Institute.
Vise andre og tillknytning
2010 (engelsk)Inngår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1879-2618, Vol. 1801, nr 8, s. 831-838Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The Niemann-Pick type Cl (NPC1) protein mediates the trafficking of cholesterol from lysosomes to other organelles. Mutations in the NPC1 gene lead to the retention of cholesterol and other lipids in the lysosomal compartment, and such defects are the basis of NPC disease. Several parallels exist between NPC disease and Alzheimers disease (AD), including altered cholesterol homeostasis, changes in the lysosomal system, neurofibrillary tangles, and increased amyloid-beta generation. How the expression of NPC1 in the human brain is affected in AD has not been investigated so far. In the present study, we measured NPC1 mRNA and protein expression in three distinct regions of the human brain, and we revealed that NPC1 expression is upregulated at both mRNA and protein levels in the hippocampus and frontal cortex of AD patients compared to control individuals. In the cerebellum, a brain region that is relatively spared in AD, no difference in NPC1 expression was detected. Similarly, murine NPC1 mRNA levels were increased in the hippocampus of 12-month-old transgenic mice expressing a familial AD form of human amyloid-beta precursor protein (APP) and presenilin-1 (APP/PS1tg) compared to 12-month-old wild type mice, whereas no change in NPC1 was detected in mouse cerebellum. Immunohistochemical analysis of human hippocampus indicated that NPC1 expression was strongest in neurons. However, in vitro studies revealed that NPC1 expression was not induced by transfecting SK-N-SH neurons with human APP or by treating them with oligomeric amyloid-beta peptide. Total cholesterol levels were reduced in hippocampus from AD patients compared to control individuals, and it is therefore possible that the increased expression of NPC1 is linked to perturbed cholesterol homeostasis in AD.

sted, utgiver, år, opplag, sider
ELSEVIER SCIENCE BV , 2010. Vol. 1801, nr 8, s. 831-838
Emneord [en]
Alzheimers disease; Niemann-Pick; Cholesterol; Lysosome; CA1; Hippocampus; Cerebellum; Frontal cortex
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-58275DOI: 10.1016/j.bbalip.2010.05.005ISI: 000279476000012OAI: oai:DiVA.org:liu-58275DiVA, id: diva2:337934
Tilgjengelig fra: 2010-08-10 Laget: 2010-08-09 Sist oppdatert: 2017-12-12

Open Access i DiVA

Fulltekst mangler i DiVA

Andre lenker

Forlagets fulltekst

Person

Kågedal, KatarinaAppelqvist, HannaAgholme, Lotta

Søk i DiVA

Av forfatter/redaktør
Kågedal, KatarinaAppelqvist, HannaAgholme, Lotta
Av organisasjonen
I samme tidsskrift
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

Søk utenfor DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric

doi
urn-nbn
Totalt: 282 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf