Interaction Between BDNF Val66Met and APOE4 on Biomarkers of Alzheimer's Disease and Cognitive Decline.
Aged
Alzheimer Disease
/ diagnostic imaging
Apolipoprotein E4
/ genetics
Brain-Derived Neurotrophic Factor
/ genetics
Cognitive Dysfunction
/ diagnostic imaging
Cohort Studies
Female
Hippocampus
/ diagnostic imaging
Humans
Longitudinal Studies
Magnetic Resonance Imaging
/ methods
Male
Methionine
/ genetics
Middle Aged
Positron-Emission Tomography
/ methods
Protein Binding
/ physiology
Valine
/ genetics
APOE4
Amyloid
BDNF
cognition
fluorodeoxyglucose F18
positron emission tomography
Journal
Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863
Informations de publication
Date de publication:
2020
2020
Historique:
pubmed:
13
10
2020
medline:
8
5
2021
entrez:
12
10
2020
Statut:
ppublish
Résumé
Whether brain-derived neurotrophic factor (BDNF) Met carriage impacts the risk or progression of Alzheimer's disease (AD) is unknown. To evaluate the interaction of BDNF Met and APOE4 carriage on cerebral metabolic rate for glucose (CMRgl), amyloid burden, hippocampus volume, and cognitive decline among cognitively unimpaired (CU) adults enrolled in the Arizona APOE cohort study. 114 CU adults (mean age 56.85 years, 38% male) with longitudinal FDG PET, magnetic resonance imaging, and cognitive measures were BDNF and APOE genotyped. A subgroup of 58 individuals also had Pittsburgh B (PiB) PET imaging. We examined baseline CMRgl, PiB PET amyloid burden, CMRgl, and hippocampus volume change over time, and rate of change in cognition over an average of 15 years. Among APOE4 carriers, BDNF Met carriers had significantly increased amyloid deposition and accelerated CMRgl decline in regions typically affected by AD, but without accompanying acceleration of cognitive decline or hippocampal volume changes and with higher baseline frontal CMRgl and slower frontal decline relative to the Val/Val group. The BDNF effects were not found among APOE4 non-carriers. Our preliminary studies suggest that there is a weak interaction between BDNF Met and APOE4 on amyloid-β plaque burden and longitudinal PET measurements of AD-related CMRgl decline in cognitively unimpaired late-middle-aged and older adults, but with no apparent effect upon rate of cognitive decline. We suggest that cognitive effects of BDNF variants may be mitigated by compensatory increases in frontal brain activity-findings that would need to be confirmed in larger studies.
Sections du résumé
BACKGROUND
Whether brain-derived neurotrophic factor (BDNF) Met carriage impacts the risk or progression of Alzheimer's disease (AD) is unknown.
OBJECTIVE
To evaluate the interaction of BDNF Met and APOE4 carriage on cerebral metabolic rate for glucose (CMRgl), amyloid burden, hippocampus volume, and cognitive decline among cognitively unimpaired (CU) adults enrolled in the Arizona APOE cohort study.
METHODS
114 CU adults (mean age 56.85 years, 38% male) with longitudinal FDG PET, magnetic resonance imaging, and cognitive measures were BDNF and APOE genotyped. A subgroup of 58 individuals also had Pittsburgh B (PiB) PET imaging. We examined baseline CMRgl, PiB PET amyloid burden, CMRgl, and hippocampus volume change over time, and rate of change in cognition over an average of 15 years.
RESULTS
Among APOE4 carriers, BDNF Met carriers had significantly increased amyloid deposition and accelerated CMRgl decline in regions typically affected by AD, but without accompanying acceleration of cognitive decline or hippocampal volume changes and with higher baseline frontal CMRgl and slower frontal decline relative to the Val/Val group. The BDNF effects were not found among APOE4 non-carriers.
CONCLUSION
Our preliminary studies suggest that there is a weak interaction between BDNF Met and APOE4 on amyloid-β plaque burden and longitudinal PET measurements of AD-related CMRgl decline in cognitively unimpaired late-middle-aged and older adults, but with no apparent effect upon rate of cognitive decline. We suggest that cognitive effects of BDNF variants may be mitigated by compensatory increases in frontal brain activity-findings that would need to be confirmed in larger studies.
Identifiants
pubmed: 33044176
pii: JAD200132
doi: 10.3233/JAD-200132
pmc: PMC10416650
mid: NIHMS1920992
doi:
Substances chimiques
Apolipoprotein E4
0
Brain-Derived Neurotrophic Factor
0
BDNF protein, human
7171WSG8A2
Methionine
AE28F7PNPL
Valine
HG18B9YRS7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
721-734Subventions
Organisme : NIA NIH HHS
ID : P30 AG019610
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG031581
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG041705
Pays : United States
Organisme : NIA NIH HHS
ID : UF1 AG046150
Pays : United States
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