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KLOTHO heterozygosi...
KLOTHO heterozygosity attenuates APOE4-related amyloid burden in preclinical AD
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Erickson, C. M. (author)
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Schultz, S. A. (author)
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Oh, J. M. (author)
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Darst, B. F. (author)
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Ma, Y. (author)
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Norton, D. (author)
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Betthauser, T. (author)
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Gallagher, C. L. (author)
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Carlsson, C. M. (author)
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Bendlin, B. B. (author)
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Asthana, S. (author)
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Hermann, B. P. (author)
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Sager, M. A. (author)
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Engelman, C. D. (author)
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Christian, B. T. (author)
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Johnson, S. C. (author)
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Dubal, D. B. (author)
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Okonkwo, O. C. (author)
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(creator_code:org_t)
- 2019-03-13
- 2019
- English.
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:16
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Objective To examine whether the KLOTHO gene variant KL-VS attenuates APOE4-associated beta-amyloid (A beta) accumulation in a late-middle-aged cohort enriched with Alzheimer disease (AD) risk factors. Three hundred nine late-middle-aged adults from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center were genotyped to determine KL-VS and APOE4 status and underwent CSF sampling (n = 238) and/or 11C-Pittsburgh compound B (PiB)-PET imaging (n = 183). Covariate-adjusted regression analyses were used to investigate whether APOE4 exerted expected effects on A beta burden. Follow-up regression analyses stratified by KL-VS genotype (i.e., noncarrier vs heterozygous; there were no homozygous individuals) evaluated whether the influence of APOE4 on A beta was different among KL-VS heterozygotes compared to noncarriers. APOE4 carriers exhibited greater A beta burden than APOE4-negative participants. This effect was stronger in CSF (t = -5.12, p < 0.001) compared with PiB-PET (t = 3.93, p < 0.001). In the stratified analyses, this APOE4 effect on A beta load was recapitulated among KL-VS noncarriers (CSF: t = -5.09, p < 0.001; PiB-PET: t = 3.77, p < 0.001). In contrast, among KL-VS heterozygotes, APOE4-positive individuals did not exhibit higher A beta burden than APOE4-negative individuals (CSF: t = -1.03, p = 0.308; PiB-PET: t = 0.92, p = 0.363). These differential APOE4 effects remained after KL-VS heterozygotes and noncarriers were matched on age and sex. In a cohort of at-risk late-middle-aged adults, KL-VS heterozygosity was associated with an abatement of APOE4-associated A beta aggregation, suggesting KL-VS heterozygosity confers protections against APOE4-linked pathways to disease onset in AD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- apolipoprotein-e
- alzheimers-disease
- functional variant
- cognitive
- decline
- epsilon-4 allele
- beta
- association
- gene
- risk
- apoe
- Neurosciences & Neurology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Neurology
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- By the author/editor
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Erickson, C. M.
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Schultz, S. A.
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Oh, J. M.
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Darst, B. F.
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Ma, Y.
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Norton, D.
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show more...
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Betthauser, T.
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Gallagher, C. L.
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Carlsson, C. M.
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Bendlin, B. B.
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Asthana, S.
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Hermann, B. P.
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Sager, M. A.
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Blennow, Kaj, 19 ...
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Zetterberg, Henr ...
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Engelman, C. D.
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Christian, B. T.
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Johnson, S. C.
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Dubal, D. B.
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Okonkwo, O. C.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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Neurology
- By the university
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University of Gothenburg