Klotho allele status is not associated with Aβ and APOE ε4–related cognitive decline in preclinical Alzheimer's disease

Tenielle Porter; Samantha C. Burnham; Lidija Milicic; Greg Savage; Paul Maruff; Yen Ying Lim; David Ames; Colin L. Masters; Ralph N. Martins; Stephanie Rainey-Smith; Christopher C. Rowe; Olivier Salvado; David Groth; Giuseppe Verdile; Victor L. Villemagne; Simon M. Laws

doi:10.1016/j.neurobiolaging.2018.12.014

Klotho allele status is not associated with Aβ and APOE ε4–related cognitive decline in preclinical Alzheimer's disease

Tenielle Porter, Samantha C. Burnham, Lidija Milicic, Greg Savage, Paul Maruff, Yen Ying Lim, David Ames, Colin L. Masters, Ralph N. Martins, Stephanie Rainey-Smith, Christopher C. Rowe, Olivier Salvado, David Groth, Giuseppe Verdile, Victor L. Villemagne, Simon M. Laws^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	162-165
Number of pages	4
Journal	Neurobiology of Aging
Volume	76
DOIs	https://doi.org/10.1016/j.neurobiolaging.2018.12.014
Publication status	Published - Apr 2019

Keywords

Klotho
KL-VS
cognition
episodic memory
amyloid-β
preclinical
Alzheimer’s disease

Access to Document

10.1016/j.neurobiolaging.2018.12.014

Link to publication in Scopus

Fingerprint Dive into the research topics of 'Klotho allele status is not associated with Aβ and APOE ε4–related cognitive decline in preclinical Alzheimer's disease'. Together they form a unique fingerprint.

Cite this

Porter, T., Burnham, S. C., Milicic, L., Savage, G., Maruff, P., Lim, Y. Y., Ames, D., Masters, C. L., Martins, R. N., Rainey-Smith, S., Rowe, C. C., Salvado, O., Groth, D., Verdile, G., Villemagne, V. L., & Laws, S. M. (2019). Klotho allele status is not associated with Aβ and APOE ε4–related cognitive decline in preclinical Alzheimer's disease. Neurobiology of Aging, 76, 162-165. https://doi.org/10.1016/j.neurobiolaging.2018.12.014

Porter, Tenielle ; Burnham, Samantha C. ; Milicic, Lidija ; Savage, Greg ; Maruff, Paul ; Lim, Yen Ying ; Ames, David ; Masters, Colin L. ; Martins, Ralph N. ; Rainey-Smith, Stephanie ; Rowe, Christopher C. ; Salvado, Olivier ; Groth, David ; Verdile, Giuseppe ; Villemagne, Victor L. ; Laws, Simon M. / Klotho allele status is not associated with Aβ and APOE ε4–related cognitive decline in preclinical Alzheimer's disease. In: Neurobiology of Aging. 2019 ; Vol. 76. pp. 162-165.

@article{43b52ec4a81d4752924f3082005df601,

title = "Klotho allele status is not associated with Aβ and APOE ε4–related cognitive decline in preclinical Alzheimer's disease",

abstract = "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.",

keywords = "Klotho, KL-VS, cognition, episodic memory, amyloid-β, preclinical, Alzheimer{\textquoteright}s disease",

author = "Tenielle Porter and Burnham, {Samantha C.} and Lidija Milicic and Greg Savage and Paul Maruff and Lim, {Yen Ying} and David Ames and Masters, {Colin L.} and Martins, {Ralph N.} and Stephanie Rainey-Smith and Rowe, {Christopher C.} and Olivier Salvado and David Groth and Giuseppe Verdile and Villemagne, {Victor L.} and Laws, {Simon M.}",

year = "2019",

month = apr,

doi = "10.1016/j.neurobiolaging.2018.12.014",

language = "English",

volume = "76",

pages = "162--165",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC",

}

Porter, T, Burnham, SC, Milicic, L, Savage, G, Maruff, P, Lim, YY, Ames, D, Masters, CL, Martins, RN, Rainey-Smith, S, Rowe, CC, Salvado, O, Groth, D, Verdile, G, Villemagne, VL & Laws, SM 2019, 'Klotho allele status is not associated with Aβ and APOE ε4–related cognitive decline in preclinical Alzheimer's disease', Neurobiology of Aging, vol. 76, pp. 162-165. https://doi.org/10.1016/j.neurobiolaging.2018.12.014

Klotho allele status is not associated with Aβ and APOE ε4–related cognitive decline in preclinical Alzheimer's disease. / Porter, Tenielle; Burnham, Samantha C.; Milicic, Lidija; Savage, Greg; Maruff, Paul; Lim, Yen Ying; Ames, David; Masters, Colin L.; Martins, Ralph N.; Rainey-Smith, Stephanie; Rowe, Christopher C.; Salvado, Olivier; Groth, David; Verdile, Giuseppe; Villemagne, Victor L.; Laws, Simon M.

In: Neurobiology of Aging, Vol. 76, 04.2019, p. 162-165.

Research output: Contribution to journal › Article › peer-review

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

VL - 76

SP - 162

EP - 165

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -