TY - JOUR
T1 - Klotho allele status is not associated with Aβ and APOE ε4–related cognitive decline in preclinical Alzheimer's disease
AU - Porter, Tenielle
AU - Burnham, Samantha C.
AU - Milicic, Lidija
AU - Savage, Greg
AU - Maruff, Paul
AU - Lim, Yen Ying
AU - Ames, David
AU - Masters, Colin L.
AU - Martins, Ralph N.
AU - Rainey-Smith, Stephanie
AU - Rowe, Christopher C.
AU - Salvado, Olivier
AU - Groth, David
AU - Verdile, Giuseppe
AU - Villemagne, Victor L.
AU - Laws, Simon M.
PY - 2019/4
Y1 - 2019/4
N2 - The longevity gene Klotho (KL), specifically the functional KL-VS variant, has previously been associated with cognition and rates of cognitive decline. This study aimed to determine whether KL-VS associations with cognition were observable in preclinical Alzheimer's disease (AD). The study also aimed to determine whether there was a combined influence of KL-VS, neocortical amyloid-β (Aβ) burden, and carriage of the apolipoprotein E (APOE) ε4 allele on cognitive decline. This study involved 581 Aβ-imaged, cognitively normal older adults, enrolled in the Australian Imaging, Biomarkers and Lifestyle Study of Aging. Linear mixed effects models revealed no significant associations between KL-VS and cognitive decline independently or in combination with Aβ burden and APOE ε4 genotype. Overall, previous associations reported between KL-VS and cognitive decline are not observed at the preclinical stages of AD. Furthermore, the results do not support the hypothesis that KL-VS has a modifying effect on Aβ burden and APOE ε4–driven cognitive decline in preclinical AD.
AB - The longevity gene Klotho (KL), specifically the functional KL-VS variant, has previously been associated with cognition and rates of cognitive decline. This study aimed to determine whether KL-VS associations with cognition were observable in preclinical Alzheimer's disease (AD). The study also aimed to determine whether there was a combined influence of KL-VS, neocortical amyloid-β (Aβ) burden, and carriage of the apolipoprotein E (APOE) ε4 allele on cognitive decline. This study involved 581 Aβ-imaged, cognitively normal older adults, enrolled in the Australian Imaging, Biomarkers and Lifestyle Study of Aging. Linear mixed effects models revealed no significant associations between KL-VS and cognitive decline independently or in combination with Aβ burden and APOE ε4 genotype. Overall, previous associations reported between KL-VS and cognitive decline are not observed at the preclinical stages of AD. Furthermore, the results do not support the hypothesis that KL-VS has a modifying effect on Aβ burden and APOE ε4–driven cognitive decline in preclinical AD.
KW - Klotho
KW - KL-VS
KW - cognition
KW - episodic memory
KW - amyloid-β
KW - preclinical
KW - Alzheimer’s disease
UR - http://www.scopus.com/inward/record.url?scp=85060897984&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2018.12.014
DO - 10.1016/j.neurobiolaging.2018.12.014
M3 - Article
C2 - 30716541
AN - SCOPUS:85060897984
SN - 0197-4580
VL - 76
SP - 162
EP - 165
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -