Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

KLOTHO heterozygosity att… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

KLOTHO heterozygosity attenuates APOE4-related amyloid burden in preclinical AD

Artikel i vetenskaplig tidskrift
Författare C. M. Erickson
S. A. Schultz
J. M. Oh
B. F. Darst
Y. Ma
D. Norton
T. Betthauser
C. L. Gallagher
C. M. Carlsson
B. B. Bendlin
S. Asthana
B. P. Hermann
M. A. Sager
Kaj Blennow
Henrik Zetterberg
C. D. Engelman
B. T. Christian
S. C. Johnson
D. B. Dubal
O. C. Okonkwo
Publicerad i Neurology
Volym 92
Nummer/häfte 16
Sidor E1878-E1889
ISSN 0028-3878
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor E1878-E1889
Språk en
Länkar dx.doi.org/10.1212/wnl.000000000000...
Ämnesord apolipoprotein-e, alzheimers-disease, functional variant, cognitive, decline, epsilon-4 allele, beta, association, gene, risk, apoe, Neurosciences & Neurology
Ämneskategorier Klinisk medicin

Sammanfattning

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.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?