Alzheimer’s disease was first described by a German neuropsychiatrist, Alois Alzheimer, who illustrated the clinical findings of dementia in a 51-year-old woman in the early 20th century.
Alzheimer’s disease is known to be the most debilitating cause of an irreversible loss of memory functions.
Being highly prevalent in Western Europe, every 14th individual over the age of 65 years in the UK is known to suffer from Alzheimer’s disease.
The pathophysiology of Alzheimer’s relies upon a series of complex biochemical events. However, recent evidence has provided us with some insight into the metabolic pathways which play a key role in the development of this chronic disease.
The kynurenine pathway is a major route involved in the metabolism of the amino acid tryptophan. This pathway is responsible for the synthesis of a few important biochemical products, including kynurenic acid (KYNA) and quinolinic acid (QUIN). Interestingly, several authors have linked these two kynurenine pathway metabolites with the neurodegenerative process of Alzheimer’s disease.
Alternative Approaches to Supporting Individuals With Dementia: Enhancing Quality of Life Through
“The most intriguing question that this research leaves us with is what has changed for the HG participants so that the gains they experienced while receiving intervention have, for the most part, been maintained? One possible explanation is that, through hypnotically induced relaxation, the HG participants had more cognitive resources available for engaging in the activities that contribute to the measures of psychosocial QOL considered in this study.“
Reference: ADEAR: “Alzheimer’s Disease Education and Referral Center, a service of the National Institute on Aging.”
To understand how these two substances are implicated in Alzheimer’s pathogenesis, it is essential to realise the contribution of glutamate and its NMDA (N-methyl D-aspartate) receptors to Alzheimer’s disease. Glutamate is known to be excitotoxic in the CNS, and its excessive activity has been declared “neurotoxic” by various neurological studies.
In light of growing evidence, quinolinic acid is associated with increased stimulation of NMDA receptors. On the contrary, kynurenic acid is recognised as an antagonist at these receptor sites. These mechanisms probably explain how QUIN and KYNA are involved in the development of neurodegenerative changes, characteristic of Alzheimer’s dementia.
This information might unlock several novel therapeutic and diagnostic gateways for effectual management of Alzheimer’s disease. Memantine is a well-known inhibitor of glutamatergic NMDA receptors and has been successfully utilised in the treatment of Alzheimer’s disease.
However, by recognising QUIN as a potential mediator of glutamate excitotoxicity, therapeutic measures can be established to effectively curb its influence in this regard. It has been proposed that QUIN can be significantly downregulated with the aid of therapeutic agents that target kynurenine pathway enzymes.
Recent evidence also suggests that some of these enzymes are characteristically upregulated during the onset of Alzheimer’s disease, which further strengthens the correlation between tryptophan catabolites and neurodegenerative disorders. In addition to QUIN, kynurenic acid analogues have also been proposed as a novel therapeutic approach to Alzheimer’s disease.
There is irrefutable research evidence that discloses the role of kynurenine metabolites in Alzheimer’s disease. Still, extensive research is warranted in determining the efficacy of certain novel therapeutic interventions via animal studies, following which human trials could be carried out in appropriate settings.
Aloysius Alzheimer (also known as Alois Alzheimer; 14 June 1864 – 19 December 1915) was a German psychiatrist and neuropathologist and a colleague of Emil Kraepelin. Alzheimer’s is credited with identifying the first published case of “presenile dementia,” which Kraepelin would later identify as Alzheimer disease. (Ref: Wikipedia)