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BDNF Val66Met in preclinical Alzheimer's disease is associated with short-term changes in episodic memory and hippocampal volume but not serum mBDNF

Published online by Cambridge University Press:  19 July 2017

Yen Ying Lim ,
Stephanie Rainey-Smith ,
Yoon Lim ,
Simon M. Laws ,
Veer Gupta ,
Tenielle Porter ,
Pierrick Bourgeat ,
David Ames ,
Christopher Fowler  and
Olivier Salvado
...Show all authors
Yen Ying Lim*
Affiliation:
The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia
Stephanie Rainey-Smith
Affiliation:
Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia
Yoon Lim
Affiliation:
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia
Simon M. Laws
Affiliation:
Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia Co-operative Research Centre for Mental Health, Carlton South, Victoria, Australia
Veer Gupta
Affiliation:
Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia
Tenielle Porter
Affiliation:
Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia Co-operative Research Centre for Mental Health, Carlton South, Victoria, Australia
Pierrick Bourgeat
Affiliation:
Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship, Australian e-Health Research Centre-BiaMedIA, Brisbane, Queensland, Australia
David Ames
Affiliation:
Academic Unit for Psychiatry of Old Age, St. Vincent's Health, The University of Melbourne, Kew, Victoria, Australia National Ageing Research Institute, Parkville, Victoria, Australia
Christopher Fowler
Affiliation:
The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia
Olivier Salvado
Affiliation:
Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship, Australian e-Health Research Centre-BiaMedIA, Brisbane, Queensland, Australia
Victor L. Villemagne
Affiliation:
The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Christopher C. Rowe
Affiliation:
Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Colin L. Masters
Affiliation:
The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia
Xin Fu Zhou
Affiliation:
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia
Ralph N. Martins
Affiliation:
Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia
Paul Maruff
Affiliation:
The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia Cogstate Ltd., Melbourne, Victoria, Australia
*
Correspondence should be addressed to: Yen Ying Lim, The Florey Institute of Neuroscience and Mental Health, 155 Oak Street, Parkville, VIC 3052, Australia. Phone: +61 3 9389 2909; Fax: +61 3 9387 5061. Email: yen.lim@florey.edu.au.
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Abstract

Background:

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36–54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months.

Methods:

Non-demented older adults (n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ– or Aβ+.

Results:

At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ– Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF.

Conclusion:

While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD.

Keywords

brain-derived neurotrophic factorAlzheimer's diseasememoryhippocampal volume
Type
Research Article
Information
International Psychogeriatrics , Volume 29 , Issue 11 , November 2017 , pp. 1825 - 1834
Copyright
Copyright © International Psychogeriatric Association 2017 

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Footnotes

*

Co-first authors on this manuscript

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