Clinical trial NCT02129452: Olfactory Neuroepithelial Tissue of Alzheimer Disease
Official title: Research of Olfactory Neuroepithelial Tissue as a Potential Biomarker of Alzheimer Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alzheimer Disease
Keywords: Alzheimer disease
Dementia
Neurodegenerative Diseases
Tauopathies
Amyloid beta Peptides
Amyloid Plaque
MicroRNAs
Early Diagnosis
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2014-05-02
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: primary care clinic

Brief summary: The purpose of this study is to evaluate the olfactory neuroepithelium as a biomarker of Alzheimer disease. The early diagnosis of Alzheimer disease is of importance for obtaining better response to treatment, but recently reported biomarkers have some limitations. Olfactory neuroepithelium tissue which is accessible through office-based biopsy without difficulty is known to reflect brain pathology that confirms the diagnosis of Alzheimer disease. This study will help in the early detection and treatment of Alzheimer disease.

Detailed description: Alzheimer disease is the most common form of dementia characterized by insidious onset and slow progression. Pathological changes in the brain of Alzheimer disease (AD) precede clinical symptoms many years, and early treatment provide better outcome. Consequently, detection of AD in early stages is needed. Biologic markers including beta-amyloid and tau protein have been studied for early diagnosis of AD. Recently remarkable biomarkers have drawn attention including CSF proteins and PIB (Amyloid-binding carbon 11-labeled Pittsburgh compound B) PET findings, but they pertain to supportive markers since they reflect brain pathology indirectly.

Postmortem studies of AD patients revealed that beta-amyloid and tau proteins are found in olfactory neuroepithelium and correlate with brain pathological changes. Olfactory neuroepithelium tissue can be obtained through office-based biopsy safely and easily by nasal endoscopy. Especially, early pathological changes of AD can be found in entorhinal cortex and piriform cortex adjacent to olfactory neuroepithelium, this study would be valuable for early detection of AD.

MicroRNAs are small, single-stranded RNA comprising about 20 nucleotides and involved in cell differentiation, growth and death. Recently the investigators reported that microRNA 206 have important role in pathomechanism of AD, thus can be new biomarker and disease-modifying therapeutic target of AD.

Study participants are enrolled from primary care clinic at department of Neurology, Seoul National University Hospital. Patients' clinical presentation, MMSE (Mini mental status exam), CDR (Clinical Dementia Rating) and ADAS-COG-K (Alzheimer Disease Assessment Scale Cognitive Subscale) are collected from routinely executed exams in the clinic. Participants are categorized into four groups according to CDR, and each group enrolls 10 patients respectively. The number of 10 patients per each group was calculated based on previous studies, costs, time and ethical perspectives.

Method for olfactory neuroepithelium biopsy was adopted from Lovell et al. (Arch Otolaryngol. 1982). Concentrations of beta-amyloid and tau proteins are analyzed from ELISA, and microRNA 206 from RT-PCR, northern blot and microarray. These data will be evaluated with clinical features and exam results of participants using general statistical methods.

Eligibility criteria: Inclusion Criteria:

* "Probable" Alzheimer disease categorized according to NINCDS-ADRDA criteria
* Written or signed informed consent obtained voluntarily from the subject, or legally acceptable representative(s) in the case of "Vulnerable subjects" with CDR more than 1

Exclusion Criteria:

* Those who are not eligible for nasal cavity biopsy due to behavioral or movement disorder
* Those who are in a hypercoagulable state or who take anticoagulant drugs
* Those who have chronic or active allergic rhinitis which interfere accurate pathological evaluation
* Those who are not suitable for the study to the judgments of researchers

Primary outcomes:
measure: Pathological evidence of Alzheimer disease in the olfactory neuroepithelium
timeFrame: Baseline at the time of enrollment. Data will be evaluated in a month.
Secondary outcomes:
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Kon Chu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee ST, Chu K, Jung KH, Kim JH, Huh JY, Yoon H, Park DK, Lim JY, Kim JM, Jeon D, Ryu H, Lee SK, Kim M, Roh JK. miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model. Ann Neurol. 2012 Aug;72(2):269-77. doi: 10.1002/ana.23588.
citation: Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239-59. doi: 10.1007/BF00308809.
citation: Arnold SE, Lee EB, Moberg PJ, Stutzbach L, Kazi H, Han LY, Lee VM, Trojanowski JQ. Olfactory epithelium amyloid-beta and paired helical filament-tau pathology in Alzheimer disease. Ann Neurol. 2010 Apr;67(4):462-9. doi: 10.1002/ana.21910.
citation: Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, Meguro K, O'brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007 Aug;6(8):734-46. doi: 10.1016/S1474-4422(07)70178-3.
citation: Attems J, Jellinger KA. Olfactory tau pathology in Alzheimer disease and mild cognitive impairment. Clin Neuropathol. 2006 Nov-Dec;25(6):265-71.
citation: Lovell MA, Jafek BW, Moran DT, Rowley JC 3rd. Biopsy of human olfactory mucosa. An instrument and a technique. Arch Otolaryngol. 1982 Apr;108(4):247-9. doi: 10.1001/archotol.1982.00790520047013.
citation: Wrobel BB, Mazza JM, Evgrafov OV, Knowles JA. Assessing the efficacy of endoscopic office olfactory biopsy sites to produce neural progenitor cell cultures for the study of neuropsychiatric disorders. Int Forum Allergy Rhinol. 2013 Feb;3(2):133-8. doi: 10.1002/alr.21080. Epub 2012 Nov 28.