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

Yen Ying Lim, Stephanie Rainey-Smith, Yoon Lim, Simon M. Laws, Veer Gupta, Tenielle Porter, Pierrick Bourgeat, David Ames, Christopher Fowler, Olivier Salvado, Victor L. Villemagne, Christopher C. Rowe, Colin L. Masters, Xin Fu Zhou, Ralph N. Martins, Paul Maruff

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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.

Original languageEnglish
Pages (from-to)1825-1834
Number of pages10
JournalInternational Psychogeriatrics
Volume29
Issue number11
DOIs
Publication statusPublished - Nov 2017
Externally publishedYes

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Episodic Memory
Brain-Derived Neurotrophic Factor
Alzheimer Disease
Serum
Homozygote
Neuroimaging
Memory Disorders
Amyloid
Alleles

Cite this

Lim, Yen Ying ; Rainey-Smith, Stephanie ; Lim, Yoon ; Laws, Simon M. ; Gupta, Veer ; Porter, Tenielle ; Bourgeat, Pierrick ; Ames, David ; Fowler, Christopher ; Salvado, Olivier ; Villemagne, Victor L. ; Rowe, Christopher C. ; Masters, Colin L. ; Zhou, Xin Fu ; Martins, Ralph N. ; Maruff, Paul. / BDNF Val66Met in preclinical Alzheimer's disease is associated with short-term changes in episodic memory and hippocampal volume but not serum mBDNF. In: International Psychogeriatrics. 2017 ; Vol. 29, No. 11. pp. 1825-1834.
@article{3845eb7907494164aa133b4044357a1b,
title = "BDNF Val66Met in preclinical Alzheimer's disease is associated with short-term changes in episodic memory and hippocampal volume but not serum mBDNF",
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 = "Alzheimer's disease, brain-derived neurotrophic factor, hippocampal volume, memory",
author = "Lim, {Yen Ying} and Stephanie Rainey-Smith and Yoon Lim and Laws, {Simon M.} and Veer Gupta and Tenielle Porter and Pierrick Bourgeat and David Ames and Christopher Fowler and Olivier Salvado and Villemagne, {Victor L.} and Rowe, {Christopher C.} and Masters, {Colin L.} and Zhou, {Xin Fu} and Martins, {Ralph N.} and Paul Maruff",
year = "2017",
month = "11",
doi = "10.1017/S1041610217001284",
language = "English",
volume = "29",
pages = "1825--1834",
journal = "International Psychogeriatrics",
issn = "1041-6102",
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Lim, YY, Rainey-Smith, S, Lim, Y, Laws, SM, Gupta, V, Porter, T, Bourgeat, P, Ames, D, Fowler, C, Salvado, O, Villemagne, VL, Rowe, CC, Masters, CL, Zhou, XF, Martins, RN & Maruff, P 2017, 'BDNF Val66Met in preclinical Alzheimer's disease is associated with short-term changes in episodic memory and hippocampal volume but not serum mBDNF' International Psychogeriatrics, vol. 29, no. 11, pp. 1825-1834. https://doi.org/10.1017/S1041610217001284

BDNF Val66Met in preclinical Alzheimer's disease is associated with short-term changes in episodic memory and hippocampal volume but not serum mBDNF. / Lim, Yen Ying; Rainey-Smith, Stephanie; Lim, Yoon; Laws, Simon M.; Gupta, Veer; Porter, Tenielle; Bourgeat, Pierrick; Ames, David; Fowler, Christopher; Salvado, Olivier; Villemagne, Victor L.; Rowe, Christopher C.; Masters, Colin L.; Zhou, Xin Fu; Martins, Ralph N.; Maruff, Paul.

In: International Psychogeriatrics, Vol. 29, No. 11, 11.2017, p. 1825-1834.

Research output: Contribution to journalArticle

TY - JOUR

T1 - BDNF Val66Met in preclinical Alzheimer's disease is associated with short-term changes in episodic memory and hippocampal volume but not serum mBDNF

AU - Lim, Yen Ying

AU - Rainey-Smith, Stephanie

AU - Lim, Yoon

AU - Laws, Simon M.

AU - Gupta, Veer

AU - Porter, Tenielle

AU - Bourgeat, Pierrick

AU - Ames, David

AU - Fowler, Christopher

AU - Salvado, Olivier

AU - Villemagne, Victor L.

AU - Rowe, Christopher C.

AU - Masters, Colin L.

AU - Zhou, Xin Fu

AU - Martins, Ralph N.

AU - Maruff, Paul

PY - 2017/11

Y1 - 2017/11

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - brain-derived neurotrophic factor

KW - hippocampal volume

KW - memory

UR - http://www.scopus.com/inward/record.url?scp=85024474222&partnerID=8YFLogxK

U2 - 10.1017/S1041610217001284

DO - 10.1017/S1041610217001284

M3 - Article

VL - 29

SP - 1825

EP - 1834

JO - International Psychogeriatrics

JF - International Psychogeriatrics

SN - 1041-6102

IS - 11

ER -