TY - JOUR
T1 - Hippocampal functional connectivity across age in an App knock-in mouse model of Alzheimer's disease
AU - Morrissey, Zachery D.
AU - Gao, Jin
AU - Zhan, Liang
AU - Li, Weiguo
AU - Fortel, Igor
AU - Saido, Takaomi
AU - Saito, Takashi
AU - Bakker, Arnold
AU - Mackin, Scott
AU - Ajilore, Olusola
AU - Lazarov, Orly
AU - Leow, Alex D.
N1 - Publisher Copyright:
Copyright © 2023 Morrissey, Gao, Zhan, Li, Fortel, Saido, Saito, Bakker, Mackin, Ajilore, Lazarov and Leow.
PY - 2023/1/12
Y1 - 2023/1/12
N2 - Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disease. The early processes of AD, however, are not fully understood and likely begin years before symptoms manifest. Importantly, disruption of the default mode network, including the hippocampus, has been implicated in AD. Methods: To examine the role of functional network connectivity changes in the early stages of AD, we performed resting-state functional magnetic resonance imaging (rs-fMRI) using a mouse model harboring three familial AD mutations (AppNL-G-F/NL-G-F knock-in, APPKI) in female mice in early, middle, and late age groups. The interhemispheric and intrahemispheric functional connectivity (FC) of the hippocampus was modeled across age. Results: We observed higher interhemispheric functional connectivity (FC) in the hippocampus across age. This was reduced, however, in APPKI mice in later age. Further, we observed loss of hemispheric asymmetry in FC in APPKI mice. Discussion: Together, this suggests that there are early changes in hippocampal FC prior to heavy onset of amyloid β plaques, and which may be clinically relevant as an early biomarker of AD.
AB - Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disease. The early processes of AD, however, are not fully understood and likely begin years before symptoms manifest. Importantly, disruption of the default mode network, including the hippocampus, has been implicated in AD. Methods: To examine the role of functional network connectivity changes in the early stages of AD, we performed resting-state functional magnetic resonance imaging (rs-fMRI) using a mouse model harboring three familial AD mutations (AppNL-G-F/NL-G-F knock-in, APPKI) in female mice in early, middle, and late age groups. The interhemispheric and intrahemispheric functional connectivity (FC) of the hippocampus was modeled across age. Results: We observed higher interhemispheric functional connectivity (FC) in the hippocampus across age. This was reduced, however, in APPKI mice in later age. Further, we observed loss of hemispheric asymmetry in FC in APPKI mice. Discussion: Together, this suggests that there are early changes in hippocampal FC prior to heavy onset of amyloid β plaques, and which may be clinically relevant as an early biomarker of AD.
KW - Alzheimer's disease
KW - App
KW - excitation-inhibition balance
KW - functional connectome
KW - hippocampus
KW - hyperexcitability
KW - interhemispheric
KW - resting-state functional magnetic resonance imaging (rs-fMRI)
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U2 - 10.3389/fnagi.2022.1085989
DO - 10.3389/fnagi.2022.1085989
M3 - Article
C2 - 36711209
AN - SCOPUS:85147110250
SN - 1663-4365
VL - 14
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
M1 - 1085989
ER -