Yen Ying Lim1, Stephanie Rainey-Smith2, Yoon Lim3, Simon M Laws2, Veer Gupta2, Tenielle Porter2, Pierrick Bourgeat4, David Ames5, Christopher Fowler1, Olivier Salvado4, Victor L Villemagne1, Christopher C Rowe6, Colin L Masters1, Xin Fu Zhou3, Ralph N Martins2, Paul Maruff1. 1. The Florey Institute,The University of Melbourne,Parkville,Victoria,Australia. 2. Centre of Excellence for Alzheimer's Disease Research and Care,Edith Cowan University,Joondalup,Western Australia,Australia. 3. School of Pharmacy and Medical Sciences,University of South Australia,Adelaide,South Australia,Australia. 4. Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship,Australian e-Health Research Centre-BiaMedIA,Brisbane,Queensland,Australia. 5. Academic Unit for Psychiatry of Old Age,St. Vincent's Health,The University of Melbourne,Kew,Victoria,Australia. 6. Department of Nuclear Medicine and Centre for PET,Austin Health,Heidelberg,Victoria,Australia.
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.
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.
Authors: Yen Ying Lim; Jason Hassenstab; Alison Goate; Anne M Fagan; Tammie L S Benzinger; Carlos Cruchaga; Eric McDade; Jasmeer Chhatwal; Johannes Levin; Martin R Farlow; Neill R Graff-Radford; Christoph Laske; Colin L Masters; Stephen Salloway; Peter Schofield; John C Morris; Paul Maruff; Randall J Bateman Journal: Ann Neurol Date: 2018-08-25 Impact factor: 10.422
Authors: Nicolai Franzmeier; Jinyi Ren; Alexander Damm; Gemma Monté-Rubio; Mercè Boada; Agustín Ruiz; Alfredo Ramirez; Frank Jessen; Emrah Düzel; Octavio Rodríguez Gómez; Tammie Benzinger; Alison Goate; Celeste M Karch; Anne M Fagan; Eric McDade; Katharina Buerger; Johannes Levin; Marco Duering; Martin Dichgans; Marc Suárez-Calvet; Christian Haass; Brian A Gordon; Yen Ying Lim; Colin L Masters; Daniel Janowitz; Cihan Catak; Steffen Wolfsgruber; Michael Wagner; Esther Milz; Sonia Moreno-Grau; Stefan Teipel; Michel J Grothe; Ingo Kilimann; Martin Rossor; Nick Fox; Christoph Laske; Jasmeer Chhatwal; Peter Falkai; Robert Perneczky; Jae-Hong Lee; Annika Spottke; Henning Boecker; Frederic Brosseron; Klaus Fliessbach; Michael T Heneka; Peter Nestor; Oliver Peters; Manuel Fuentes; Felix Menne; Josef Priller; Eike J Spruth; Christiana Franke; Anja Schneider; Christine Westerteicher; Oliver Speck; Jens Wiltfang; Claudia Bartels; Miguel Ángel Araque Caballero; Coraline Metzger; Daniel Bittner; Stephen Salloway; Adrian Danek; Jason Hassenstab; Igor Yakushev; Peter R Schofield; John C Morris; Randall J Bateman; Michael Ewers Journal: Mol Psychiatry Date: 2019-03-21 Impact factor: 15.992
Authors: Christopher Fowler; Stephanie R Rainey-Smith; Sabine Bird; Julia Bomke; Pierrick Bourgeat; Belinda M Brown; Samantha C Burnham; Ashley I Bush; Carolyn Chadunow; Steven Collins; James Doecke; Vincent Doré; Kathryn A Ellis; Lis Evered; Amir Fazlollahi; Jurgen Fripp; Samantha L Gardener; Simon Gibson; Robert Grenfell; Elise Harrison; Richard Head; Liang Jin; Adrian Kamer; Fiona Lamb; Nicola T Lautenschlager; Simon M Laws; Qiao-Xin Li; Lucy Lim; Yen Ying Lim; Andrea Louey; S Lance Macaulay; Lucy Mackintosh; Ralph N Martins; Paul Maruff; Colin L Masters; Simon McBride; Lidija Milicic; Madeline Peretti; Kelly Pertile; Tenielle Porter; Morgan Radler; Alan Rembach; Joanne Robertson; Mark Rodrigues; Christopher C Rowe; Rebecca Rumble; Olivier Salvado; Greg Savage; Brendan Silbert; Magdalene Soh; Hamid R Sohrabi; Kevin Taddei; Tania Taddei; Christine Thai; Brett Trounson; Regan Tyrrell; Michael Vacher; Shiji Varghese; Victor L Villemagne; Michael Weinborn; Michael Woodward; Ying Xia; David Ames Journal: J Alzheimers Dis Rep Date: 2021-06-03