Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
21543606
TITLE
Common Alzheimer's disease risk variant within the CLU gene affects white matter microstructure in young adults.
ABSTRACT
There is a strong genetic risk for late-onset Alzheimer's disease (AD), but so far few gene variants have been identified that reliably contribute to that risk. A newly confirmed genetic risk allele C of the clusterin (CLU) gene variant rs11136000 is carried by ∼88% of Caucasians. The C allele confers a 1.16 greater odds of developing late-onset AD than the T allele. AD patients have reductions in regional white matter integrity. We evaluated whether the CLU risk variant was similarly associated with lower white matter integrity in healthy young humans. Evidence of early brain differences would offer a target for intervention decades before symptom onset. We scanned 398 healthy young adults (mean age, 23.6 ± 2.2 years) with diffusion tensor imaging, a variation of magnetic resonance imaging sensitive to white matter integrity in the living brain. We assessed genetic associations using mixed-model regression at each point in the brain to map the profile of these associations with white matter integrity. Each C allele copy of the CLU variant was associated with lower fractional anisotropy--a widely accepted measure of white matter integrity--in multiple brain regions, including several known to degenerate in AD. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. Young healthy carriers of the CLU gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing AD later in life.
DATE PUBLISHED
2011 May 4
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2011/05/06 06:00
pubmed 2011/05/06 06:00
medline 2011/08/06 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Braskie MN Braskie Meredith N MN Laboratory of Neuro Imaging, Department of Neurology, University of California, School of Medicine, Los Angeles, California 90095, USA.
Jahanshad N Jahanshad Neda N
Stein JL Stein Jason L JL
Barysheva M Barysheva Marina M
McMahon KL McMahon Katie L KL
de Zubicaray GI de Zubicaray Greig I GI
Martin NG Martin Nicholas G NG
Wright MJ Wright Margaret J MJ
Ringman JM Ringman John M JM
Toga AW Toga Arthur W AW
Thompson PM Thompson Paul M PM
INVESTIGATORS
JOURNAL
VOLUME: 31
ISSUE: 18
TITLE: The Journal of neuroscience : the official journal of the Society for Neuroscience
ISOABBREVIATION: J. Neurosci.
YEAR: 2011
MONTH: May
DAY: 4
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1529-2401
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: J Neurosci
COUNTRY: United States
ISSNLINKING: 0270-6474
NLMUNIQUEID: 8102140
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
1F31MH087061 NIMH NIH HHS United States
F31 MH087061 NIMH NIH HHS United States
R01 AG040060 NIA NIH HHS United States
R01 EB007813 NIBIB NIH HHS United States
R01 EB007813 NIBIB NIH HHS United States
R01 EB008281 NIBIB NIH HHS United States
R01 EB008281 NIBIB NIH HHS United States
R01 EB008432 NIBIB NIH HHS United States
R01 EB008432 NIBIB NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
T15 LM007356 NLM NIH HHS United States
T15 LM07356 NLM NIH HHS United States
T32 NS048004 NINDS NIH HHS United States
T32 NS048004:05 NINDS NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Alleles
Alzheimer Disease pathology
Analysis of Variance pathology
Brain pathology
Brain Mapping pathology
Clusterin genetics
Diffusion Tensor Imaging genetics
Diseases in Twins pathology
Female pathology
Genotype pathology
Humans pathology
Image Processing, Computer-Assisted pathology
Male pathology
Nerve Fibers, Myelinated pathology
Neuropsychological Tests pathology
Risk pathology
Twins pathology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 CLU protein, human
0 Clusterin
OTHER ID's
OTHERID SOURCE
NIHMS293342 NLM
PMC3176803 NLM