Tau pathology is associated with postsynaptic metabotropic glutamate receptor 5 (mGluR5) in early Alzheimer's disease in a sex-specific manner

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-02-25 DOI:10.1002/alz.70004

Yan Wang, Jie Wang, Xing Chen, Zengping Lin, Zhiwen You, Kun He, Tengfei Guo, Jun Zhao, Qi Huang, Ruiqing Ni, Yihui Guan, Binyin Li, Fang Xie

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引用次数: 0

Abstract

INTRODUCTION

To investigate the associations of metabotropic glutamate receptor 5 (mGluR5) with tau deposition and cognitive ability in patients with early Alzheimer's disease (AD).

METHODS

Twenty-six cognitively impaired (CI) and 14 cognitively unimpaired (CU) individuals underwent mGluR5 positron emission tomography (PET) ([¹⁸F]PSS232), amyloid PET ([¹⁸F]florbetapir), and tau PET ([¹⁸F]MK6240), and neuropsychological assessment. The relationships among mGluR5 availability, tau deposition, and neuropsychological assessment were analyzed using Spearman's correlation and mediation analyses.

RESULTS

CI patients had lower mGluR5 in the hippocampus than CU (standardized uptake value ratio [SUVr]: 2.03 ± 0.25 vs 1.79 ± 0.17, p = 0.003). Hippocampal mGluR5 was negatively associated with hippocampal tau deposition (r = −.46, p = 0.003) and positively associated with cognitive performance, but only in women. Hippocampal tau deposition mediated the effect of mGluR5 on cognitive performance.

DISCUSSION

Reduced hippocampal mGluR5 is negatively related with tau deposition in most cortical regions and positively associated with cognitive performance, making it a promising biomarker for AD diagnosis and therapy.

Highlights

Cognitively impaired (CI) patients exhibited lower metabotropic glutamate receptor 5 (mGluR5) availability in the hippocampus than cognitively unimpaired (CU) subjects.
Hippocampal mGluR5 availability was negatively associated with tau deposition in widespread cortex.
Hippocampal mGluR5 availability was positively associated with cognitive performance.
The close association of mGluR5 with tau and cognition performance exists only in females.
Tau pathology mediated the relationship between mGluR5 availability and cognition.

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.