Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 146-154 |
| Number of pages | 9 |
| Journal | Neurobiology of Aging |
| Volume | 108 |
| DOIs | |
| Publication status | Published - 1 Dec 2021 |
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BDNF-Met polymorphism and amyloid-beta in relation to cognitive decline in cognitively normal elderly : the SCIENCe project. / van den Bosch, Karlijn A.; Verberk, Inge M. W.; Ebenau, Jarith L. et al.
In: Neurobiology of Aging, Vol. 108, 01.12.2021, p. 146-154.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - BDNF-Met polymorphism and amyloid-beta in relation to cognitive decline in cognitively normal elderly
T2 - the SCIENCe project
AU - van den Bosch, Karlijn A.
AU - Verberk, Inge M. W.
AU - Ebenau, Jarith L.
AU - van der Lee, Sven J.
AU - Jansen, Iris E.
AU - Prins, Niels D.
AU - Scheltens, Philip
AU - Teunissen, Charlotte E.
AU - van der Flier, Wiesje M.
N1 - Funding Information: K.A.v.d.B., I.M.W.V., J.L.E., S.J.vd.L, and I.J. have nothing to disclose. N.D.P is consultant to Boehringer Ingelheim, Aribio, and Amylyx. He is co-PI of a study with Fuji Film Toyama Chemical. He is CEO and co-owner of the Brain Research Center, The Netherlands. P.S. has received consultancy fees (paid to the institution) from AC Immune, Alkermes, Alnylam, Alzheon, Anavex, Biogen, Brainstorm Cell, Cortexyme, Denali, EIP, ImmunoBrain Checkpoint, GemVax, Genentech, Green Valley, Novartis, Novo Nordisk, PeopleBio, Renew LLC, Roche. He is PI of studies with AC Immune, CogRx, FUJI-film/Toyama, IONIS, UCB, and Vivoryon. He is a part-time employee of Life Sciences Partners Amsterdam. He serves on the board of Brain Research Center and New Amsterdam Pharma. Research of C.E.T. is supported by the European Commission (Marie Curie International Training Network, grant agreement No 860197 (MIRIADE), and JPND), Health Holland, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands, Alzheimer Association. C.E.T and W.M.v.d.F are recipients of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health∼Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). ABOARD also receives funding from Edwin Bouw Fonds and Gieskes-Strijbisfonds. Research programs of W.M.vd.F. have been funded by ZonMW, NWO, EU-FP7, EU-JPND, Alzheimer Nederland, CardioVascular Onderzoek Nederland, Health∼Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Pasman stichting, Biogen MA Inc, Boehringer Ingelheim, Life-MI, AVID, Roche BV, Fujifilm, Combinostics. Funding Information: Alzheimer Center Amsterdam is supported by Alzheimer Nederland and Stichting VUmc fonds. K.A.vd.B, I.M.W.V. and J.L.E. are supported by research grants from Gieskes-Strijbis Fonds, stichting Dioraphte, and Alzheimer Nederland (NL-17004). Genotyping was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW projectnumber 733051061). C.E.T. is supported by the European Commission (Marie Curie International Training Network, JPND), the Dutch Research Council (ZonMW), The Weston Brain Institute, Alzheimer Netherland. W.M.v.d.F. holds the Pasman chair. Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. We thank Hans Heijst for performing the plasma measurements in the neurochemistry laboratory of the Amsterdam UMC, VUmc. Publisher Copyright: © 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Brain-derived neurotrophic factor (BNDF) plays a role in synapse integrity. We investigated in 398 cognitively normal adults (60±8years, 41% female, MMSE=28±1) the joint association of the Val66Met polymorphism of the BDNF gene (Met+/-) and plasma BDNF levels and abnormal cerebrospinal fluid (CSF) amyloid-beta status (A+/-) with cognitive decline and dementia risk. Age-, sex- and education-adjusted linear mixed models showed that compared to Met-A-, Met+A+ showed steeper decline on tests of global cognition, memory, language, attention and executive functioning, while Met-A+ showed steeper decline on a smaller number of tests. There were no associations between Met+A- and cognitive decline. Cox models showed that compared to Met-A-, Met+A+ participants were at increased risk of dementia (HR=8.8, 95%CI: 2.8–27.9), as were Met-A+ participants (HR=6.5, 95%CI: 2.2–19.5). Lower plasma BDNF was associated with an increased risk of progression to dementia in the A+ participants. Our results imply that Met-carriage on top of amyloid-beta pathology might increase rate of cognitive decline to dementia.
AB - Brain-derived neurotrophic factor (BNDF) plays a role in synapse integrity. We investigated in 398 cognitively normal adults (60±8years, 41% female, MMSE=28±1) the joint association of the Val66Met polymorphism of the BDNF gene (Met+/-) and plasma BDNF levels and abnormal cerebrospinal fluid (CSF) amyloid-beta status (A+/-) with cognitive decline and dementia risk. Age-, sex- and education-adjusted linear mixed models showed that compared to Met-A-, Met+A+ showed steeper decline on tests of global cognition, memory, language, attention and executive functioning, while Met-A+ showed steeper decline on a smaller number of tests. There were no associations between Met+A- and cognitive decline. Cox models showed that compared to Met-A-, Met+A+ participants were at increased risk of dementia (HR=8.8, 95%CI: 2.8–27.9), as were Met-A+ participants (HR=6.5, 95%CI: 2.2–19.5). Lower plasma BDNF was associated with an increased risk of progression to dementia in the A+ participants. Our results imply that Met-carriage on top of amyloid-beta pathology might increase rate of cognitive decline to dementia.
KW - Alzheimer's disease
KW - Amyloid-beta
KW - BDNF
KW - Subjective Cognitive Decline
KW - Val66Met
UR - http://www.scopus.com/inward/record.url?scp=85115996158&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2021.08.018
DO - 10.1016/j.neurobiolaging.2021.08.018
M3 - Article
C2 - 34601245
VL - 108
SP - 146
EP - 154
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
ER -