The human olfactory system in two proteinopathies: Alzheimer’s and Parkinson’s diseases

Abstract

Alzheimer’s and Parkinson’s diseases are the most prevalent neurodegenerative disorders. Their etiologies are idiopathic, and treatments are symptomatic and orientated towards cognitive or motor deficits. Neuropathologically, both are proteinopathies with pathological aggregates (plaques of amyloid-β peptide and neurofibrillary tangles of tau protein in Alzheimer’s disease, and Lewy bodies mostly composed of α-synuclein in Parkinson’s disease). These deposits appear in the nervous system in a predictable and accumulative sequence with six neuropathological stages. Both disorders present a long prodromal period, characterized by preclinical signs including hyposmia. Interestingly, the olfactory system, particularly the anterior olfactory nucleus, is initially and preferentially affected by the pathology. Cerebral atrophy revealed by magnetic resonance imaging must be complemented by histological analyses to ascertain whether neuronal and/or glial loss or neuropil remodeling are responsible for volumetric changes. It has been proposed that these proteinopathies could act in a prion-like manner in which a misfolded protein would be able to force native proteins into pathogenic folding (seeding), which then propagates through neurons and glia (spreading). Existing data have been examined to establish why some neuronal populations are vulnerable while others are resistant to pathology and to what extent glia prevent and/or facilitate proteinopathy spreading. Connectomic approaches reveal a number of hubs in the olfactory system (anterior olfactory nucleus, olfactory entorhinal cortex and cortical amygdala) that are key interconnectors with the main hubs (the entorhinal–hippocampal–cortical and amygdala–dorsal motor vagal nucleus) of network dysfunction in Alzheimer’s and Parkinson’s diseases.

Astrogliosis and sexually dimorphic neurodegeneration and microgliosis in the olfactory bulb in Parkinson’s disease

“…Interestingly, α-synuclein (α-syn) aggregates (Lewy bodies and neurites) have been described in the olfactory bulb (OB) at early neuropathological stages of the disease 8,9 . In fact, these deposits are particularly conspicuous in the OB [10][11][12][13] . A previous study in our laboratory showed that Lewy bodies and Lewy neurites were present in mitral cells and the inner plexiform layer and they were particularly abundant in the anterior olfactory nucleus.…”

Association of Olfactory Impairment and Postoperative Cognitive Dysfunction in Elderly Patients

“…N = 30,*p < 0.05 vs. the control group; #p < 0.05 vs. pre-anesthesia. in both AD and PD patients (Kubota et al, 2020;Ubeda-Bañon et al, 2020). In the previous studies on AD patients with olfactory impairment, it was found that the level of serum acetylcholine was significantly reduced, which not only affects memory function, but also plays an important role in the olfactory system, indicating that the reduction of acetylcholine may also be a cause of the olfactory impairment in AD patients (Beach et al, 2000).…”

Olfactory function in patients with obstructive sleep apnea and the effect of positive airway pressure treatment: a systematic review and meta-analysis

“…The other mechanism can be explained by the neurocognitive effects of OSA. Previous studies have shown that neurocognitive dysfunction leads to olfactory malfunctioning in patients with neurodegenerative diseases such as Alzheimer’s and Parkinson’s [ 21 – 23 ]. Similarly, patients with OSA have impaired cognitive functions as a result of sleep fragmentation, sleep loss, arousals, intermittent hypoxia, and hypoxia-reoxygenation episodes [ 24 – 26 ].…”