Asymmetric left–right hippocampal glutamatergic modulation of cognitive control in ApoE‐isoform subjects is unrelated to neuroinflammation

• Published in: The European journal of neuroscience Vol. 54; no. 4; pp. 5310 - 5326
• Main Authors: Zhang, Hui, Chiu, Pui Wai, Ip, Isaac, Liu, Tianyin, Wong, Gloria Hoi Yan, Song, You‐Qiang, Wong, Savio Wai Ho, Herrup, Karl, Mak, Henry Ka Fung
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01.08.2021; John Wiley and Sons Inc
• Subjects: Adult; Alzheimer Disease; ApoE4; Apolipoprotein E; Apolipoprotein E4; Apolipoprotein E4 - genetics; Brain; Brain mapping; Cognition; Cognitive ability; Functional magnetic resonance imaging; glutamatergic system; Glutamatergic transmission; Hippocampus; Humans; Hyperemia; Inflammation; Isoforms; Magnetic Resonance Imaging; Magnetic resonance spectroscopy; Molecular and Synaptic Mechanisms; Neuroimaging; Research Report; Synaptic plasticity; Synaptic transmission; magnetic resonance spectroscopy; functional magnetic resonance imaging; ApoE4; glutamatergic system
• ISSN: 0953-816X; 1460-9568; 1460-9568
• DOI: 10.1111/ejn.15399

The glutamatergic cycle is essential in modulating memory processing by the hippocampal circuitry. Our combined proton magnetic resonance spectroscopy (1H‐MRS) and task‐based functional magnetic resonance imaging (fMRI) study (using face‐name paired‐associates encoding and retrieval task) of a cognitively normal cohort of 67 healthy adults (18 ApoE4 carriers and 49 non‐ApoE4 carriers) found altered patterns of relationships between glutamatergic‐modulated synaptic signalling and neuronal activity or functional hyperaemia in the ApoE4 isoforms. Our study highlighted the asymmetric left–right hippocampal glutamatergic system in modulating neuronal activities in ApoE4 carriers versus non‐carriers. Such brain differentiation might be developmental cognitive advantages or compensatory due to impaired synaptic integrity and plasticity in ApoE4 carriers. As there was no difference in myoinositol levels measured by MRS between the ApoE4 and non‐ApoE4 subgroups, the mechanism is unlikely to be a response to neuroinflammation. Asymmetric left–right hippocampal glutamatergic system in modulating neuronal activities in ApoE4 carriers versus non‐carriers. We speculated that such brain differentiation might have developmental cognitive advantages or compensatory due to impaired synaptic integrity and plasticity in ApoE4 carriers.