Abstract
INTRODUCTION
Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the pathophysiological mechanism of Alzheimer’s disease (AD).
METHODS
Ten cognitively impaired (CI) individuals and 10 healthy controls (HCs) underwent [18F]SynVesT-1 and [18F]PSS232 positron emission tomography (PET)/magnetic resonance to assess synaptic density and mGluR5 availability. The associations between mGluR5 availability and synaptic density were examined. A mediation analysis was performed to investigate the possible mediating effects of mGluR5 availability and synaptic loss on the relationship between amyloid deposition and cognition.
RESULTS
CI patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and cognition.
CONCLUSIONS
Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD and are closely linked.
Highlights
Cognitively impaired patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs.
Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD.
Regional synaptic density was closely associated with regional mGluR5 availability.
mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and global cognition.
With further research, modulating mGluR5 availability might be a potential therapeutic strategy for improving synaptic function in AD.
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This post is Copyright: Jie Wang,
Qi Huang,
Kun He,
Junpeng Li,
Tengfei Guo,
Yang Yang,
Zengping Lin,
Songye Li,
Greet Vanderlinden,
Yiyun Huang,
Koen Van Laere,
Yihui Guan,
Qihao Guo,
Ruiqing Ni,
Binying Li,
Fang Xie | April 18, 2024