Kynurenic Acid Levels are Increased in the CSF of Alzheimer's Disease Patients.

Marta González-Sánchez,Jose Antonio Molina Arjona,Eva Carro,Sara Llamas-Velasco,Adolfo López de Munain,Alberto Villarejo-Galende,Alejandro Herrero-San Martín,M.-Pilar Marco,Arantzazu Narváez,Fernando Bartolome,David Andrés Pérez-Martínez,Alberto Lleó Bisa,Desiree Antequera,Elena Domínguez,Javier Jiménez,Montserrat Rodríguez-Núñez

doi:10.3390/biom10040571

Abstract

Kynurenic acid (KYNA) is a product of the tryptophan (TRP) metabolism via the kynurenine pathway (KP). This pathway is activated in neurodegenerative disorders, such as Alzheimer´s disease (AD). KYNA is primarily produced by astrocytes and is considered neuroprotective. Thus, altered KYNA levels may suggest an inflammatory response. Very recently, significant increases in KYNA levels were reported in cerebrospinal fluid (CSF) from AD patients compared with normal controls. In this study, we assessed the accuracy of KYNA in CSF for the classification of patients with AD, cognitively healthy controls, and patients with a variety of other neurodegenerative diseases, including frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and progressive supranuclear palsy (PSP). Averaged KYNA concentration in CSF was higher in patients with AD when compared with healthy subjects and with all the other differentially diagnosed groups. There were no significant differences in KYNA levels in CSF between any other neurodegenerative groups and controls. These results suggest a specific increase in KYNA concentration in CSF from AD patients not seen in other neurodegenerative diseases.

Highlights

Alzheimer’s disease (AD) is a complex and progressive neurodegenerative disorder that represents one of the major health problems in the world [1]
132 subjects were included in this study: (i) elderly non-demented subjects classified as controls (n = 23); (ii) patients with mild cognitive impairment due to AD (MCI) (n = 24); (iii) probable mild AD (n = 41); (iv) moderate–severe AD (n = 20); (v) frontotemporal dementia (FTD) (n = 8); (vi) amyotrophic lateral sclerosis (ALS) (n = 8); and (vii) progressive supranuclear palsy (PSP) (n = 8)
We report in a new and large cohort, increased kynurenic acid (KYNA) levels in cerebrospinal fluid (CSF) from AD patients compared to healthy subjects, including prodromal stages of the disease

Summary

Introduction

Alzheimer’s disease (AD) is a complex and progressive neurodegenerative disorder that represents one of the major health problems in the world [1]. The consequence of the brain accumulation of Aβ and tau can be detected by analyzing the levels of Aβ42 peptide (the most neurotoxic isoform of Aβ) and total tau (t-tau) protein in the cerebrospinal fluid (CSF) of AD patients. The exact initiating and pathophysiological AD-initiating factors remain unknown, but the majority of AD-related research is based on the amyloid cascade and tau hypotheses In addition to these theories, different pathological mechanisms, such as mitochondrial dysfunction, glutamate excitotoxicity, and neuroinflammation have been implicated in AD [2,3,4,5,6,7,8]. Any imbalance in the KP and subsequently in the production of TRP metabolites may cause neuronal damage, giving rise to multiple physiological and neurological impairments [16,17]

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