COMT val158met is not associated with Aβ-amyloid and APOE ε4 related cognitive decline in cognitively normal older adults

Tenielle Porter^{1

2}, Samantha C Burnham^{3

4}, Lidija Milicic^{1

2}, Greg Savage⁵, Paul Maruff^{6

7}, Hamid R Sohrabi⁴, Madeline Peretti^{1

2}, Yen Ying Lim⁶, Michael Weinborn^{4

8}, David Ames^{9

10}, Colin L Masters⁶, Ralph N Martins⁴, Stephanie Rainey-Smith⁴, Christopher C Rowe^{11

12}, Olivier Salvado¹³, David Groth¹⁴, Giuseppe Verdile^{4

14}, Victor L Villemagne^{6

11

12}, Simon M Laws^{1

2

14}

Affiliations

¹ Collaborative Genomics Group, Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Western Australia, Australia.
² Cooperative Research Centre for Mental Health, Australia.
³ CSIRO Health and Biosecurity, Parkville 3052, Victoria, Australia.
⁴ Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Western Australia, Australia.
⁵ ARC Centre of Excellence in Cognition and its Disorders, Department of Psychology, Macquarie University, North Ryde 2113, NSW, Australia.
⁶ The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville 3052, Victoria, Australia.
⁷ CogState Ltd., Melbourne 3000, Victoria, Australia.
⁸ School of Psychology, University of Western Australia, Crawley 6009, Western Australia, Australia.
⁹ Academic Unit for Psychiatry of Old Age, St. Vincent's Health, The University of Melbourne, Kew 3101, Victoria, Australia.
¹⁰ National Ageing Research Institute, Parkville 3052, Victoria, Australia.
¹¹ Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg 3084, Victoria, Australia.
¹² Department of Medicine, Austin Health, The University of Melbourne, Heidelberg 3084, Victoria, Australia.
¹³ CSIRO Health and Biosecurity/Australian e-Health Research Centre, Herston 4029, Queensland, Australia.
¹⁴ School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley 6102, Western Australia, Australia.

PMID: 31080907
PMCID: PMC6506436
DOI: 10.1016/j.ibror.2019.05.001

COMT val158met is not associated with Aβ-amyloid and APOE ε4 related cognitive decline in cognitively normal older adults

Tenielle Porter et al. IBRO Rep. 2019.

. 2019 May 2:6:147-152.

doi: 10.1016/j.ibror.2019.05.001. eCollection 2019 Jun.

Authors

Affiliations

¹ Collaborative Genomics Group, Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Western Australia, Australia.
² Cooperative Research Centre for Mental Health, Australia.
³ CSIRO Health and Biosecurity, Parkville 3052, Victoria, Australia.
⁴ Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Western Australia, Australia.
⁵ ARC Centre of Excellence in Cognition and its Disorders, Department of Psychology, Macquarie University, North Ryde 2113, NSW, Australia.
⁶ The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville 3052, Victoria, Australia.
⁷ CogState Ltd., Melbourne 3000, Victoria, Australia.
⁸ School of Psychology, University of Western Australia, Crawley 6009, Western Australia, Australia.
⁹ Academic Unit for Psychiatry of Old Age, St. Vincent's Health, The University of Melbourne, Kew 3101, Victoria, Australia.
¹⁰ National Ageing Research Institute, Parkville 3052, Victoria, Australia.
¹¹ Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg 3084, Victoria, Australia.
¹² Department of Medicine, Austin Health, The University of Melbourne, Heidelberg 3084, Victoria, Australia.
¹³ CSIRO Health and Biosecurity/Australian e-Health Research Centre, Herston 4029, Queensland, Australia.
¹⁴ School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley 6102, Western Australia, Australia.

PMID: 31080907
PMCID: PMC6506436
DOI: 10.1016/j.ibror.2019.05.001

Abstract

The non-synonymous single nucleotide polymorphism (SNP), Val158Met within the Catechol-O-methyltransferase (COMT) gene has been associated with altered levels of cognition and memory performance in cognitively normal adults. This study aimed to investigate the independent and interactional effects of COMT Val158Met on cognitive performance. In particular, it was hypothesised that COMT Val158Met would modify the effect of neocortical Aβ-amyloid (Aβ) accumulation and carriage of the apolipoprotein E (APOE) ε4 allele on cognition in preclinical Alzheimer's disease (AD). In 598 cognitively normal older adults with known neocortical Aβ levels, linear mixed modelling revealed no significant independent or interactional associations between COMT Val158Met and cognitive decline. These findings do not support previous associations between COMT Val158Met and cognitive performance and suggest this variant does not influence Aβ-amyloid or APOE ε4 driven cognitive decline in a well characterised cohort of cognitively normal older adults.

Keywords: Aβ-amyloid; COMT; Catechol-O-methyltransferase; Cognitive decline; Episodic memory.

PubMed Disclaimer

Cited by

Deciphering the Effect of Different Genetic Variants on Hippocampal Subfield Volumes in the General Population.
Kirchner K, Garvert L, Wittfeld K, Ameling S, Bülow R, Meyer Zu Schwabedissen H, Nauck M, Völzke H, Grabe HJ, Van der Auwera S. Kirchner K, et al. Int J Mol Sci. 2023 Jan 6;24(2):1120. doi: 10.3390/ijms24021120. Int J Mol Sci. 2023. PMID: 36674637 Free PMC article.
Relationships of Cerebrospinal Fluid Alzheimer's Disease Biomarkers and COMT, DBH, and MAOB Single Nucleotide Polymorphisms.
Babić Leko M, Nikolac Perković M, Klepac N, Švob Štrac D, Borovečki F, Pivac N, Hof PR, Šimić G. Babić Leko M, et al. J Alzheimers Dis. 2020;73(1):135-145. doi: 10.3233/JAD-190991. J Alzheimers Dis. 2020. PMID: 31771069 Free PMC article.
Meta-Analysis of the Effects of the Catechol-O-Methyltransferase Val158/108Met Polymorphism on Parkinson's Disease Susceptibility and Cognitive Dysfunction.
Tang C, Wang W, Shi M, Zhang N, Zhou X, Li X, Ma C, Chen G, Xiang J, Gao D. Tang C, et al. Front Genet. 2019 Jul 12;10:644. doi: 10.3389/fgene.2019.00644. eCollection 2019. Front Genet. 2019. PMID: 31354790 Free PMC article.
Fifteen Years of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study: Progress and Observations from 2,359 Older Adults Spanning the Spectrum from Cognitive Normality to Alzheimer's Disease.
Fowler C, Rainey-Smith SR, Bird S, Bomke J, Bourgeat P, Brown BM, Burnham SC, Bush AI, Chadunow C, Collins S, Doecke J, Doré V, Ellis KA, Evered L, Fazlollahi A, Fripp J, Gardener SL, Gibson S, Grenfell R, Harrison E, Head R, Jin L, Kamer A, Lamb F, Lautenschlager NT, Laws SM, Li QX, Lim L, Lim YY, Louey A, Macaulay SL, Mackintosh L, Martins RN, Maruff P, Masters CL, McBride S, Milicic L, Peretti M, Pertile K, Porter T, Radler M, Rembach A, Robertson J, Rodrigues M, Rowe CC, Rumble R, Salvado O, Savage G, Silbert B, Soh M, Sohrabi HR, Taddei K, Taddei T, Thai C, Trounson B, Tyrrell R, Vacher M, Varghese S, Villemagne VL, Weinborn M, Woodward M, Xia Y, Ames D; the AIBL investigators. Fowler C, et al. J Alzheimers Dis Rep. 2021 Jun 3;5(1):443-468. doi: 10.3233/ADR-210005. eCollection 2021. J Alzheimers Dis Rep. 2021. PMID: 34368630 Free PMC article.

References

1. Barnett J.H., Scoriels L., Munafo M.R. Meta-analysis of the cognitive effects of the catechol-O-methyltransferase gene Val158/108Met polymorphism. Biol. Psychiatry. 2008;64(2):137–144. - PubMed
1. Bellander M., Backman L., Liu T., Schjeide B.M., Bertram L., Schmiedek F., Lindenberger U., Lovden M. Lower baseline performance but greater plasticity of working memory for carriers of the val allele of the COMT Val(1)(5)(8)Met polymorphism. Neuropsychology. 2015;29(2):247–254. - PubMed
1. Bilder R.M., Volavka J., Czobor P., Malhotra A.K., Kennedy J.L., Ni X., Goldman R.S., Hoptman M.J., Sheitman B., Lindenmayer J.P., Citrome L., McEvoy J.P., Kunz M., Chakos M., Cooper T.B., Lieberman J.A. Neurocognitive correlates of the COMT Val(158)Met polymorphism in chronic schizophrenia. Biol. Psychiatry. 2002;52(7):701–707. - PubMed
1. Blanchard M.M., Chamberlain S.R., Roiser J., Robbins T.W., Muller U. Effects of two dopamine-modulating genes (DAT1 9/10 and COMT Val/Met) on n-back working memory performance in healthy volunteers. Psychol. Med. 2011;41(3):611–618. - PubMed
1. Bolton J.L., Marioni R.E., Deary I.J., Harris S.E., Stewart M.C., Murray G.D., Fowkes F.G., Price J.F. Association between polymorphisms of the dopamine receptor D2 and catechol-o-methyl transferase genes and cognitive function. Behav. Genet. 2010;40(5):630–638. - PubMed

LinkOut - more resources

Full Text Sources
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

COMT val158met is not associated with Aβ-amyloid and APOE ε4 related cognitive decline in cognitively normal older adults

Affiliations

COMT val158met is not associated with Aβ-amyloid and APOE ε4 related cognitive decline in cognitively normal older adults

Authors

Affiliations

Abstract

Similar articles

Cited by

References

LinkOut - more resources

Full Text Sources

Miscellaneous

Abstract

Similar articles

Cited by

References

Related information

LinkOut - more resources

Full Text Sources

Miscellaneous