Journal
ACTA NEUROPATHOLOGICA
Volume 127, Issue 4, Pages 459-475Publisher
SPRINGER
DOI: 10.1007/s00401-014-1261-7
Keywords
Olfactory system; Olfactory bulb; Olfactory dysfunction; Pathology; Alzheimer disease; Parkinson disease; Neurodegenerative disorders
Categories
Funding
- National Institute for Health Research (NIHR) Biomedical Research Centre for Ageing and Age-related disease
- Biomedical Research Unit for Lewy body dementia based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University [R:CH/ML/0712]
- Dunhill Medical Trust [R173/1110]
- Newcastle Brain Tissue Resource
- UK Medical Research Council [G0400074]
- Brains for Dementia Research, a joint venture between Alzheimer's Society and Alzheimer's Research UK
- Alzheimers Research UK [ART-EG2010A-1] Funding Source: researchfish
- Medical Research Council [G1100540, MR/L016451/1, G0900652, G0502157, G0400074] Funding Source: researchfish
- The Dunhill Medical Trust [R173/1110] Funding Source: researchfish
- MRC [G0400074, G0502157, G0900652, G1100540, MR/L016451/1] Funding Source: UKRI
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available