The Olfactory System as Marker of Neurodegeneration in Aging, Neurological and Neuropsychiatric Disorders

Abstract

Research studies that focus on understanding the onset of neurodegenerative pathology and therapeutic interventions to inhibit its causative factors, have shown a crucial role of olfactory bulb neurons as they transmit and propagate nerve impulses to higher cortical and limbic structures. In rodent models, removal of the olfactory bulb results in pathology of the frontal cortex that shows striking similarity with frontal cortex features of patients diagnosed with neurodegenerative disorders. Widely different approaches involving behavioral symptom analysis, histopathological and molecular alterations, genetic and environmental influences, along with age-related alterations in cellular pathways, indicate a strong correlation of olfactory dysfunction and neurodegeneration. Indeed, declining olfactory acuity and olfactory deficits emerge either as the very first symptoms or as prodromal symptoms of progressing neurodegeneration of classical conditions. Olfactory dysfunction has been associated with most neurodegenerative, neuropsychiatric, and communication disorders. Evidence revealing the dual molecular function of the olfactory receptor neurons at dendritic and axonal ends indicates the significance of olfactory processing pathways that come under environmental pressure right from the onset. Here, we review findings that olfactory bulb neuronal processing serves as a marker of neuropsychiatric and neurodegenerative disorders.

Aging-Related Alterations of Glymphatic Transport in Rat: In vivo Magnetic Resonance Imaging and Kinetic Study

“…The olfactory sensory nerves serve as a CSF outflow pathway ( Norwood et al, 2019 ). Age-dependent decrease in the number of olfactory sensory neurons ( Mobley et al, 2014 ) and decline in neurogenesis capacity ( Enwere et al, 2004 ; Child et al, 2018 ), and neurodegeneration ( Hussain et al, 2018 ; Bhatia-Dey and Heinbockel, 2021 ) that parallel with OI ( Mobley et al, 2014 ) may increase the resistance to CSF flow ( Albeck et al, 1998 ; Norwood et al, 2019 ), negatively affecting solute drainage through the olfactory efflux route. Olfactory deficit has been linked to advanced physiological brain aging ( Devanand et al, 2015 ; Park et al, 2021 ) and has been associated with the forthcoming neurodegenerative disorders ( Baba et al, 2012 ; Yoo et al, 2019 ), although the mechanism behind these associations remains to be explored.…”

SARS-CoV-2 neurotropism and other possible causes of olfactory disorders in COVID-19

“…Indeed it is considered one of the clinical markers of the early stages of the disease [49,50]. Damage to brain tissue in the area of the limbic system and the olfactory bulb in the early stages of the disease can lead to long-term hearing impairment, which is characteristic of both Parkinson's and Alzheimer's and can occur in the course of COVID-19 [51,52]. Given the previously mentioned similarities between neurodegenerative diseases and COVID-19, long-term olfactory loss with cognitive and emotional disturbances in the course of SARS-CoV-2 may be a symptom of dementia in the course of neurodegenerative processes [53].…”

Chemosensory Ability and Sensitivity in Health and Disease: Epigenetic Regulation and COVID-19

“…In rodents, odorant receptor proteins localized in olfactory sensory neurons of the olfactory epithelium lining the nasal cavity, are the first molecules exposed to inhaled odorants [ 99 ]. In contrast to developing olfactory sensory neurons that transiently express multiple olfactory receptor genes, mature olfactory sensory neurons strictly follow a one-neuron–one-olfactory receptor expression pattern [ 100 , 101 ].…”