Toggle Main Menu Toggle Search

Open Access padlockePrints

Olfactory bulb involvement in neurodegenerative diseases

Lookup NU author(s): Professor Johannes Attems, Dr Lauren Walker

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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, alpha-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 HP tau, A beta, and alpha Syn pathology correlated and increased significantly (P < 0.001) with increasing neuritic Braak stages, Thal A beta 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.


Publication metadata

Author(s): Attems J, Walker L, Jellinger KA

Publication type: Review

Publication status: Published

Journal: Acta Neuropathologica

Year: 2014

Volume: 127

Issue: 4

Pages: 459-475

Print publication date: 20/02/2014

ISSN (print): 0001-6322

ISSN (electronic): 1432-0533

Publisher: SPRINGER

URL: http://dx.doi.org/10.1007/s00401-014-1261-7

DOI: 10.1007/s00401-014-1261-7


Actions

Find at Newcastle University icon    Link to this publication


Share