title: Plasma levels of 24S-hydroxycholesterol reflect brain volumes in patients without objective cognitive impairment but not in those with Alzheimer's disease.
abstract: OBJECTIVE
  Cholesterol has been linked to Alzheimer's disease (AD) and plasma 24S-hydroxycholesterol (24OHC) has been suggested as a surrogate marker for brain cholesterol metabolism. This study investigates the relation of 24OHC as well as markers of extracerebral cholesterol homeostasis (lanosterol, lathosterol, cholesterol, LDL-C, HDL-C and 27-hydroxycholesterol) with brain volumes in memory clinic patients.
  
  
  METHODS
  96 patients (33 with subjective cognitive impairment--SCI; 36 with mild cognitive impairment--MCI; 27 with AD) referred to the Memory Clinic at Karolinska University Hospital, Sweden. Plasma assessments were done by isotope dilution-mass spectrometry. MRI measurements were done using custom-made software BMAP (imaging laboratory, Karolinska Institutet), running on HERMES platform.
  
  
  RESULTS
  Ratios of 24-hydroxycholesterol, 27-hydroxycholesterol, lanosterol and lathosterol to cholesterol (R_24OHC, R_27OHC, R_lanosterol and R_lathosterol) were significantly lower in patients with AD. In the whole population, after controlling for age, sex, APOE genotype and statins, R_24OHC was positively related to gray matter (GM) fraction. However, when groups were considered separately, the relation to GM volume, GM and parenchymal fractions was significant in the SCI group only (p<0.05). There was a significant positive association between cholesterol and white matter (WM) volume, WM and parenchymal fractions in patients with AD.
  
  
  CONCLUSIONS
  Plasma R_24OHC was lower in patients with AD, but R_24OHC was significantly related to brain volumes in the control group only. One reason may be the previously demonstrated abnormal expression of cholesterol 24S-hydroxylase in astrocytes in AD, which may limit the usefulness of this plasma marker in this specific disease. The findings on cholesterol agree with previous reports of decreasing plasma cholesterol levels in AD patients, suggesting a CNS-mediated effect on extracerebral cholesterol homeostasis.
authors: Department of Neurology, University of Kuopio, Kuopio, Finland. alina.solomon@uku.fi
authors: Alina
authors: A
authors: Solomon
authors: Valerio
authors: V
authors: Leoni
authors: Miia
authors: M
authors: Kivipelto
authors: Ariadna
authors: A
authors: Besga
authors: Anne Rita
authors: AR
authors: Oksengård
authors: Per
authors: P
authors: Julin
authors: Leif
authors: L
authors: Svensson
authors: Lars-Olof
authors: LO
authors: Wahlund
authors: Niels
authors: N
authors: Andreasen
authors: Bengt
authors: B
authors: Winblad
authors: Hilkka
authors: H
authors: Soininen
authors: Ingemar
authors: I
authors: Björkhem
mesh_terms: D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000473:pathology*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003072:Cognition Disorders / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D005260:Female; D005838:Genotype; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D007810:Lanosterol / Q000097:blood; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D012737:Sex Factors
chemical_list: D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006888:Hydroxycholesterols; D007810:Lanosterol; C044563:24-hydroxycholesterol; C076996:27-hydroxycholesterol; C001521:lathosterol; D002784:Cholesterol