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.

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.

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 care clinic