Assessment of olfactory function in MAPT-associated neurodegenerative disease reveals odor-identification irreproducibility as a non-disease-specific, general characteristic of olfactory dysfunction

Katerina Markopoulou, Bruce A Chase, Piotr Robowski, Audrey Strongosky, Ewa Narozańska, Emilia J. Sitek, Mariusz Berdynski, Maria Barcikowska, Matt C. Baker, Rosa Rademakers, Jarosław Sławek, Christine Klein, Katja Hückelheim, Meike Kasten, Zbigniew K. Wszolek

Research output: Contribution to journalArticle

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Abstract

Olfactory dysfunction is associated with normal aging, multiple neurodegenerative disorders, including Parkinson's disease, Lewy body disease and Alzheimer's disease, and other diseases such as diabetes, sleep apnea and the autoimmune disease myasthenia gravis. The wide spectrum of neurodegenerative disorders associated with olfactory dysfunction suggests different, potentially overlapping, underlying pathophysiologies. Studying olfactory dysfunction in presymptomatic carriers of mutations known to cause familial parkinsonism provides unique opportunities to understand the role of genetic factors, delineate the salient characteristics of the onset of olfactory dysfunction, and understand when it starts relative to motor and cognitive symptoms. We evaluated olfactory dysfunction in 28 carriers of two MAPT mutations (p.N279K, p.P301L), which cause frontotemporal dementia with parkinsonism, using the University of Pennsylvania Smell Identification Test. Olfactory dysfunction in carriers does not appear to be allele specific, but is strongly age-dependent and precedes symptomatic onset. Severe olfactory dysfunction, however, is not a fully penetrant trait at the time of symptom onset. Principal component analysis revealed that olfactory dysfunction is not odor-class specific, even though individual odor responses cluster kindred members according to genetic and disease status. Strikingly, carriers with incipient olfactory dysfunction show poor inter-test consistency among the sets of odors identified incorrectly in successive replicate tests, even before severe olfactory dysfunction appears. Furthermore, when 78 individuals without neurodegenerative disease and 14 individuals with sporadic Parkinson's disease were evaluated twice at a one-year interval using the Brief Smell Identification Test, the majority also showed inconsistency in the sets of odors they identified incorrectly, independent of age and cognitive status. While these findings may reflect the limitations of these tests used and the sample sizes, olfactory dysfunction appears to be associated with the inability to identify odors reliably and consistently, not with the loss of an ability to identify specific odors. Irreproducibility in odor identification appears to be a nondisease-specific, general feature of olfactory dysfunction that is accelerated or accentuated in neurodegenerative disease. It may reflect a fundamental organizational principle of the olfactory system, which is more "error-prone" than other sensory systems.

Original languageEnglish (US)
Article numbere0165112
JournalPloS one
Volume11
Issue number11
DOIs
StatePublished - Nov 1 2016

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Neurodegenerative diseases
neurodegenerative diseases
Odors
Neurodegenerative Diseases
odors
Smell
Parkinson disease
smell
testing
signs and symptoms (animals and humans)
Parkinson Disease
sleep apnea
mutation
Lewy Body Disease
Frontotemporal Dementia
Neurobehavioral Manifestations
Mutation
Inborn Genetic Diseases
sensory system
Aptitude

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Assessment of olfactory function in MAPT-associated neurodegenerative disease reveals odor-identification irreproducibility as a non-disease-specific, general characteristic of olfactory dysfunction. / Markopoulou, Katerina; Chase, Bruce A; Robowski, Piotr; Strongosky, Audrey; Narozańska, Ewa; Sitek, Emilia J.; Berdynski, Mariusz; Barcikowska, Maria; Baker, Matt C.; Rademakers, Rosa; Sławek, Jarosław; Klein, Christine; Hückelheim, Katja; Kasten, Meike; Wszolek, Zbigniew K.

In: PloS one, Vol. 11, No. 11, e0165112, 01.11.2016.

Research output: Contribution to journalArticle

Markopoulou, K, Chase, BA, Robowski, P, Strongosky, A, Narozańska, E, Sitek, EJ, Berdynski, M, Barcikowska, M, Baker, MC, Rademakers, R, Sławek, J, Klein, C, Hückelheim, K, Kasten, M & Wszolek, ZK 2016, 'Assessment of olfactory function in MAPT-associated neurodegenerative disease reveals odor-identification irreproducibility as a non-disease-specific, general characteristic of olfactory dysfunction', PloS one, vol. 11, no. 11, e0165112. https://doi.org/10.1371/journal.pone.0165112
Markopoulou, Katerina ; Chase, Bruce A ; Robowski, Piotr ; Strongosky, Audrey ; Narozańska, Ewa ; Sitek, Emilia J. ; Berdynski, Mariusz ; Barcikowska, Maria ; Baker, Matt C. ; Rademakers, Rosa ; Sławek, Jarosław ; Klein, Christine ; Hückelheim, Katja ; Kasten, Meike ; Wszolek, Zbigniew K. / Assessment of olfactory function in MAPT-associated neurodegenerative disease reveals odor-identification irreproducibility as a non-disease-specific, general characteristic of olfactory dysfunction. In: PloS one. 2016 ; Vol. 11, No. 11.
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