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Olfactory bulb involvement in neurodegenerative diseases

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Abstract

Olfactory dysfunction is a common and early symptom of many neurodegenerative diseases, particularly of Parkinson’s disease and other synucleinopathies, Alzheimer’s disease (AD), and mild cognitive impairment heralding its progression to dementia. The neuropathologic changes of olfactory dysfunction in neurodegenerative diseases may involve the olfactory epithelium, olfactory bulb/tract, primary olfactory cortices, and their secondary targets. Olfactory dysfunction is related to deposition of pathological proteins, α-synuclein, hyperphosphorylated tau protein, and neurofilament protein in these areas, featured by neurofibrillary tangles, Lewy bodies and neurites inducing a complex cascade of molecular processes including oxidative damage, neuroinflammation, and cytosolic disruption of cellular processes leading to cell death. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with severe anosmia. Recent studies of olfactory dysfunction have focused its potential as an early biomarker for the diagnosis of neurodegenerative disorders and their disease progression. Here, we summarize the current knowledge on neuropathological and pathophysiological changes of the olfactory system in the most frequent neurodegenerative diseases, in particular AD and synucleinopathies. We also present neuropathological findings in the olfactory bulb and tract in a large autopsy cohort (n = 536, 57.8 % female, mean age 81.3 years). The severity of olfactory bulb HPτ, Aβ, and αSyn pathology correlated and increased significantly (P < 0.001) with increasing neuritic Braak stages, Thal Aβ phases, and cerebral Lewy body pathology, respectively. Hence, further studies are warranted to investigate the potential role of olfactory biopsies (possibly restricted to the olfactory epithelium) in the diagnostic process of neurodegenerative diseases in particular in clinical drug trials to identify subjects showing early, preclinical stages of neurodegeneration and to stratify clinically impaired cohorts according to the underlying cerebral neuropathology.

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Acknowledgments

The research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre for Ageing and Age-related disease and the Biomedical Research Unit for Lewy body dementia based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University (R:CH/ML/0712). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Part of this study was supported by the Dunhill Medical Trust (R173/1110). Tissue for this study was provided by the Newcastle Brain Tissue Resource, which is funded in part by a grant from the UK Medical Research Council (G0400074) and by Brains for Dementia Research, a joint venture between Alzheimer’s Society and Alzheimer’s Research UK.

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  1. Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK

    Johannes Attems & Lauren Walker

  2. Institute of Clinical Neurobiology, Medical University Vienna, Kenyongasse 18, 1070, Vienna, Austria

    Kurt A. Jellinger

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  1. Johannes Attems
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Correspondence to Kurt A. Jellinger.

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Dedicated to the memory of Hans A. Kretzschmar who faded away much too early.

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Attems, J., Walker, L. & Jellinger, K.A. Olfactory bulb involvement in neurodegenerative diseases. Acta Neuropathol 127, 459–475 (2014). https://doi.org/10.1007/s00401-014-1261-7

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