Olfactory Neuroepithelial Tissue of Alzheimer Disease
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease
Study type: Observational

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.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        primary care clinic
      
Biospecimen description: 
      Tissue including olfactory neuroepithelium from nasal cavity
    
Keywords: Alzheimer disease; Dementia; Neurodegenerative Diseases; Tauopathies; Amyloid beta Peptides; Amyloid Plaque; MicroRNAs; Early Diagnosis