Alzheimer Disease, Smell Dysfunction, Smell Loss
Conditions
Keywords
act-seq, nasal biopsy, RNA-seq
Brief summary
This research study aims to investigate the function of the olfactory lining in the nasal cavity and its potential alterations in both healthy and diseased conditions. The olfactory lining is involved in the sense of smell. The purpose of this study is to collect tissue from the nasal cavity.
Detailed description
The purpose of this study is to analyze cell populations active in human olfactory tissue in health and disease. This is a prospective study. Healthy participants or participants with known disease processes that may impact olfaction, such as Alzheimer's, inflammatory conditions, aging, or post-viral smell loss, will be included. Olfaction will be measured using standard psychophysical testing. Biopsies of the olfactory lining in the nasal cavity may be obtained in the otolaryngology clinic or the operating room, if the patient is having an unrelated endoscopic nasal surgery, and may be obtained using a punch technique or a cytology brush. Before biopsies, some patients may be asked to sniff an odor substance (such as lavender, mint, citrus, or cloves) briefly, to stimulate olfactory cells. Biopsies will be processed for assays in the PI's lab, including histology, primary culture assays, flow cytometry assays, or transcriptomic profiling.
Interventions
DIAGNOSTIC_TESTolfactory testing
Patients will undergo smell testing, using the Smell Identification Test (Sensonics), a validated widely-used 40-item "scratch-and-sniff" style psychophysical test to determine olfactory function.
OTHEROdor stimulation
subset of patients will be asked to sniff a specific odor for about an hour, using commercially available "odor pens" (Sniffin' Sticks or Sensonics). These odor pens are widely used for olfactory training therapy, a treatment designed to help people with some forms of smell loss; they are also used in psychophysical olfactory testing.
PROCEDUREOlfactory biopsy
Biopsy involves a simple cytology brush technique of the lining of the nose in a region called the olfactory cleft, using a nasal endoscope, and can be done in clinic or in the operating room at the time of a nasal surgery. Topical oxymetazoline and tetracaine spray is applied to the nasal cavity, a rigid nasal endoscopy (0-degree 4 mm endoscope, Karl Storz) is performed to visualize the olfactory cleft, and a small nasal cytology brush biopsy (Hobbs Medical)is performed by swabbing and rotating brush gently in the olfactory cleft. Cytology sample is placed into a buffer (Hibernate-E, Thermo Fisher)on ice for transport to the research lab.
Sponsors
Duke University
National Institute on Deafness and Other Communication Disorders (NIDCD)
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Group 1: Alzheimer's study Inclusion Criteria: * Between the ages of 18 and 80 * Pre-clinical AD (this cohort consists of subjects who have normal cognitive testing and function, but have positive AD biomarkers); * Symptomatic AD (a confirmed diagnosis of Alzheimer's or dementia who are capable of understanding and signing the consent document)
Exclusion criteria
* Advanced Alzheimer's/dementia * Self-reported or known allergy to Afrin or Tetracain HCL (or related class of drugs) * Active Rhinosinusitis symptoms * Other known sinonasal disease history that would preclude biopsy (i.e prior sinus or skull base surgery directly impacting this anatomic region, sinonasal neoplasm in this anatomic region, olfactory cleft polyps) * Parkinson's disease * Unable or willing to complete the nasal endoscopy procedure. * Unable to read or speak English * Unable to provide legally effective consent Group 2: Act-seq study or Non-AD controls Inclusion Criteria: * Age 18 years or older * Patients being seen for rhinology or olfactory disorders * Patients having unrelated endoscopic nasal surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Transcription state changes in olfactory cells | study is planned for completion over 5 years | Using single cell RNA-sequencing, olfactory epithelial cell populations will be analyzed for changes in coherent gene expression programs from subjects in different environmental conditions. |
Countries
United States
Contacts
CONTACTMaria J Manson, MBA
CONTACTBradley J Goldstein, MD, PhD
PRINCIPAL_INVESTIGATORBradley Goldstein, MD, PhD
Duke University
Outcome results
None listed