Elevated Glutamate and Glutamine Levels in the Cerebrospinal Fluid of Patients With Probable Alzheimer's Disease and Depression

Caroline Madeira,Carlos Otávio Brandão,Jerson Laks,Taylor Reis,Rogerio Panizzutti,Sergio T Ferreira,Charles Vargas-Lopes

doi:10.3389/fpsyt.2018.00561

Caroline Madeira, Carlos Otávio Brandão + Show 5 more

Open Access

https://doi.org/10.3389/fpsyt.2018.00561

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Journal: Frontiers in psychiatry	Publication Date: Nov 6, 2018
Citations: 131	License type: CC BY 4.0

Affiliation: Universidade Federal do Rio de Janeiro

Abstract

Recent evidence suggests that Alzheimer's disease (AD) and depression share common mechanisms of pathogenesis. In particular, deregulation of glutamate-mediated excitatory signaling may play a role in brain dysfunction in both AD and depression. We have investigated levels of glutamate and its precursor glutamine in the cerebrospinal fluid (CSF) of patients with a diagnosis of probable AD or major depression compared to healthy controls and patients with hydrocephalus. Patients with probable AD or major depression showed significantly increased CSF levels of glutamate and glutamine compared to healthy controls or hydrocephalus patients. Furthermore, CSF glutamate and glutamine levels were inversely correlated to the amyloid tau index, a biomarker for AD. Results suggest that glutamate and glutamine should be further explored as potential CSF biomarkers for AD and depression.

Highlights

Epidemiological and clinical studies suggest an association between Alzheimer’s disease (AD) and depression [1, 2], the latter being a risk factor for development of AD and other forms of dementia [3,4,5]
We report increased cerebrospinal fluid (CSF) levels of glutamate and glutamine in AD and major depression compared to healthy controls and to patients with normal pressure hydrocephalus
Lower Mini-Mental State Examination (MMSE) and Innotest amyloid tau index (IATI) scores were correlated with higher glutamate and glutamine levels in our study cohort

Summary

Introduction

Epidemiological and clinical studies suggest an association between Alzheimer’s disease (AD) and depression [1, 2], the latter being a risk factor for development of AD and other forms of dementia [3,4,5]. About half of the patients with major depression show cognitive impairment that can be persistent and last even after remission of the acute phase of symptoms [6]. This could mean cognitive impairment precedes or predisposes to depression or, alternatively, that depression produces persistent cognitive deficits [6, 7]. Recent studies have further suggested that similar pathogenic mechanisms may underlie cognitive changes in depression and in AD.

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