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Markers of cholesterol metabolism in the brain show stronger associations with cerebrovascular disease than Alzheimer's disease.

TitleMarkers of cholesterol metabolism in the brain show stronger associations with cerebrovascular disease than Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2012
AuthorsHughes, TM, Kuller, LH, Lopez, OL, Becker, JT, Evans, RW, Sutton-Tyrrell, K, Rosano, C
JournalJ Alzheimers Dis
Volume30
Issue1
Pagination53-61
Date Published2012
ISSN1875-8908
KeywordsAge Factors, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoprotein E4, Brain, Cerebrovascular Disorders, Cognition Disorders, Cohort Studies, Female, Humans, Hydroxycholesterols, Magnetic Resonance Imaging, Male, Retrospective Studies
Abstract<p>Cholesterol metabolism is believed to play a role in the development of Alzheimer's disease (AD). Oxysterol metabolites of cholesterol, 24S-hydroxycholesterol (24-OHC, a brain-derived oxysterol) and 27-hydroxycholesterol (27-OHC, a peripherally derived oxysterol) cross the blood brain barrier and have been associated with AD. We investigated whether oxysterols were associated with markers of cerebrovascular disease prior to the onset of cognitive impairment. Oxysterols were quantified in 105 participants (average age: 80 ± 4 years) from the Pittsburgh Cardiovascular Health Study Cognition Study who remained cognitively normal at blood draw in 2002, had MRI in 1992 and 1998, and annual cognitive assessment for incident AD and mild cognitive impairment made by consensus conference between 1998 and 2010. Higher plasma levels of 24-OHC were associated with age, gender, the presence of high grade white matter hyperintensities, and brain infarcts on prior MRI. Participants with higher plasma 24-OHC and a greater ratio of 24-OHC/27-OHC were also more likely to develop incident cognitive impairment over 8 years of follow-up. Higher levels of 24-OHC suggest increased cholesterol metabolism occurring in the brains of participants with cerebrovascular disease prior to the onset of cognitive impairment. Measurement of oxysterols may provide information about cholesterol metabolism and brain disease over the cognitive impairment process.</p>
DOI10.3233/JAD-2012-111460
Alternate JournalJ. Alzheimers Dis.
PubMed ID22377780
PubMed Central IDPMC3348402
Grant ListP30 AG024827 / AG / NIA NIH HHS / United States
AG023269 / AG / NIA NIH HHS / United States
R01 HL075366 / HL / NHLBI NIH HHS / United States
AG027058 / AG / NIA NIH HHS / United States
AG15928 / AG / NIA NIH HHS / United States
R01 AG015928-02 / AG / NIA NIH HHS / United States
N01 HC085081 / HC / NHLBI NIH HHS / United States
N01-HC85086 / HC / NHLBI NIH HHS / United States
R01 AG015928 / AG / NIA NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01 HC075150 / HC / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
N01 HC085083 / HC / NHLBI NIH HHS / United States
AG020098 / AG / NIA NIH HHS / United States
R01 AG027058-04 / AG / NIA NIH HHS / United States
T32HL083825 / HL / NHLBI NIH HHS / United States
R56 AG020098 / AG / NIA NIH HHS / United States
P30-AG-024827 / AG / NIA NIH HHS / United States
P50 AG005133-29 / AG / NIA NIH HHS / United States
N01 HC085085 / HC / NHLBI NIH HHS / United States
R01 HL080295-07 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
T32 HL083825-05 / HL / NHLBI NIH HHS / United States
R01 HL075366-05 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
N01 HC085082 / HC / NHLBI NIH HHS / United States
N01 HC085080 / HC / NHLBI NIH HHS / United States
HL075366 / HL / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
AG05133 / AG / NIA NIH HHS / United States
N01 HC055222 / HC / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
R01 AG020098-09 / AG / NIA NIH HHS / United States
P50 AG005133 / AG / NIA NIH HHS / United States
R01 HL080295 / HL / NHLBI NIH HHS / United States
N01 HC085084 / HC / NHLBI NIH HHS / United States
R01 AG020098 / AG / NIA NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
N01-HC-85239 / HC / NHLBI NIH HHS / United States
AG20098 / AG / NIA NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01 HC085079 / HC / NHLBI NIH HHS / United States
T32 HL083825 / HL / NHLBI NIH HHS / United States
R01 AG027058 / AG / NIA NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States