Crownlands Observing Progression With Neurons Study (CROWN-I)

Crownlands Observing Progression With Neurons I (CROWN-I)

The CROWN-I Study is an observational study to learn about molecular features of Alzheimer's disease (AD) and mild cognitive impairment (MCI). The primary objective is to identify the molecular and genetic modules that differentiate patient subtypes and predict progression of AD. Participants will visit clinical sites to donate samples multiple times and perform virtual and in-person clinical assessments.

Study Overview

• Status: Recruiting
• Conditions: Mild Cognitive Impairment (MCI); Alzheimer s Disease

Detailed Description

Neurological diseases are difficult to characterize at the molecular level because disease-relevant tissue is rarely available in clinical practice. As a result, precision approaches in neurology have historically relied on indirect measures, including clinical assessments, neuroimaging, and biomarkers measured in blood, cerebrospinal fluid (CSF), and other biofluids. Although these tools have advanced diagnosis and monitoring, they provide limited access to neuron-specific and high-dimensional molecular information.

CROWN-I is a data-intensive longitudinal observational study designed to expand molecular and clinical characterization of Alzheimer's disease (AD) and mild cognitive impairment (MCI). The CROWN-I Study aims to track multiple high-dimensional molecular readouts in participants with AD and MCI as well as cognitively normal controls (CN). Participants will provide biospecimens at multiple time points and complete medical histories and clinical and cognitive assessments.

The study will analyze molecular signatures from olfactory neuron samples and blood. These data will be used to differentiate participant subgroups and may inform new therapeutic and clinical strategies for disease-modifying medicines.

• Study Type: Observational
• Enrollment (Estimated): 160

Contacts and Locations

• Study Contact: Name: Mason Sanfilippo, MS; Phone Number: (415) 623-8635; Email: m.sanfilippo@crownlands.com

Study Locations

• United States
  • Maryland
    • Germantown, Maryland, United States, 20876
      • Recruiting
      • Capital Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

United States

Description

Inclusion Criteria:

• Informed consent provided by the participant or, where applicable, Legally Authorized Representative (LAR) or other substitute decision-maker where permitted by applicable law, as described in Section 8.2.
• Male or female, age ≥ 55 years at Screening.
• Fluency of subject and study partner in English sufficient to complete all cognitive and self-report assessments without interpreter assistance.
• Adequate visual and auditory acuity (with correction permitted) sufficient to complete neuropsychological testing.
• Not pregnant or lactating.
• Medications stable ≥ 4 weeks before screening.
• GDS-15 < 6 (i.e., 0-5 inclusive; no current significant depression).
• Available study partner who has known the participant for ≥ 12 months, maintains ~10+ hours per week of in-person or telephone contact, and is willing to attend study visits and complete informant-rated assessments.
• Willing to complete olfactory brushing, smell testing, and venous blood draw.
• Willing to commit to baseline and follow-up visits across study duration.
• In the opinion of the Investigator, able to comply with the protocol-specified visit schedule and procedures for the full study duration.

Exclusion Criteria:

• Current or active clinically significant neurological disorder (in the opinion of the Investigator) other than the disorders in the study arms, including but not limited to:
• Parkinson's disease, dementia with Lewy bodies, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, Huntington's disease, prion disease, multi-infarct dementia, normal pressure hydrocephalus, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, significant head trauma with persistent deficits, or known structural brain abnormalities.
• Active or unstable major psychiatric illness (DSM-5 schizophrenia spectrum, bipolar I, or severe major depressive disorder with active suicidality) within 6 months prior to Screening; history of schizophrenia at any time.
• Psychotic features, agitation, or behavioral problems within the last 3 months that could interfere with protocol compliance.
• Current substance use disorder (DSM-5 moderate or severe), or alcohol use disorder within 24 months prior to Screening.
• Active malignancy under treatment, or malignancy with expected survival < 30 months (excluding non-melanoma skin cancer and localized prostate cancer on active surveillance).
• Participation in studies collecting neuropsychological measures more than once per year.
• Presence of previous nasal surgery or other anatomical abnormalities that could interfere with the procedure on both sides of the nose, at the discretion of the clinician administering the Olfactory Brushing.
• Active respiratory infection or recent history of respiratory infection within the past two weeks.
• Known allergy or adverse reaction to topical anesthetics or decongestants used in the study (e.g., lidocaine, tetracaine, oxymetazoline).
• Any other medical or psychiatric condition or lab abnormality that, in the opinion of the Investigator, might preclude participation or render the participant unsuitable for study enrollment.

Cognitively Normal (CN) Additional Inclusion Criteria (CN)

• No subjective cognitive complaint reported by participant AND no cognitive -complaint reported by study partner.
• No current or prior clinical diagnosis of MCI, Alzheimer's disease, or any other dementia, and no current clinical diagnosis of a neurological or neuropsychiatric disease.
• MMSE score ≥ 27 / 30 at Screening.
• Global Clinical Dementia Rating (CDR) = 0 at Screening.
• CDR Sum of Boxes (CDR-SB) = 0 at Screening.
• Performance within 1.0 standard deviation of demographically adjusted norms on the Rey Auditory Verbal Learning Test (RAVLT) Delayed Recall.

Additional Exclusion Criteria (CN)

• Current or prior use of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) or memantine for any indication.
• Current or prior use of anti-amyloid monoclonal antibody disease-modifying therapy (aducanumab, lecanemab, donanemab, or any investigational anti-amyloid mAb).

Mild Cognitive Impairment (MCI) Additional Inclusion Criteria (MCI)

• Subjective cognitive complaint reported by participant OR partner-verified memory complaint reported by study partner.
• MMSE score ≥ 24 and ≤ 30 at Screening.
• Global CDR = 0.5 at Screening.
• CDR-SB ≥ 0.5 and < 3 at Screening; CDR Memory Box ≥ 0.5.
• Performance ≥ 1.5 standard deviations below demographically adjusted norms on the RAVLT Delayed Recall (or equivalent episodic memory criterion per the Petersen / NIA-AA MCI framework).
• Preserved general functional ability such that the participant does not meet criteria for dementia (i.e., does not meet AD criteria in Section 7.3).

Alzheimer's Disease (AD) Additional Inclusion Criteria (AD)

• Confirmed clinical diagnosis of probable Alzheimer's disease by a qualified specialist (cognitive neurologist, geriatric psychiatrist, or equivalent), consistent with NIA-AA 2011 (McKhann et al.) or NIA-AA 2018 Research Framework biological criteria.
• MMSE score ≥ 16 and ≤ 26 at Screening.
• Global CDR ≥ 1 at Screening.
• CDR-SB ≥ 3 at Screening.
• CDR Memory Box score ≥ 0.5 at Screening.
• Partner-verified history of progressive cognitive decline of ≥ 6 months duration.
• Functional impairment consistent with dementia, as documented on the CDR Functional Domains (Community Affairs, Home & Hobbies, Personal Care); participant able to complete protocol.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Alzheimer's disease (AD); Participants with diagnosed Alzheimer's disease
Mild cognitive impairment (MCI); Participants with diagnosed or apparent MCI
Cognitively normal; Participants who are cognitively normal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of change in CDR-SB	The primary clinical outcomes are longitudinal changes from baseline in Clinical Dementia Rating - Sum of Boxes as administered by a qualified clinician. The CDR-SB evaluates six domains (memory, orientation, judgment, community affairs, home/hobbies, and personal care) for a total score ranging from 0 to 18, with increases indicating worsening impairment.	From enrollment to the end of the observational period at 18 months or final visit
Change in olfactory neuron transcriptomic profile	Change from baseline in olfactory neurons measured by Gateway in transcriptomic pathways associated with AD by human genetics.	From enrollment to the end of the observational period at 18 months or final visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in p-tau217 in blood plasma	Change in quantitative levels of p-tau217 in blood plasma over the study observational period.	From enrollment to the end of the observational period at 18 months or final visit
Change in Aβ42/Aβ40 in blood plasma	Change in quantitative levels of amyloid β-peptide (Aβ) 42 : amyloid β-peptide (Aβ) 40 ratio in blood plasma over the study observational period.	From enrollment to the end of the observational period at 18 months or final visit
Change in whole blood transcriptomic profile	Change from baseline in transcriptomic pathways associated with AD by human genetics in whole blood.	From enrollment to the end of the observational period at 18 months or other endpoint
Change in plasma proteomic profile	Change from baseline in proteomic pathways associated with AD in plasma.	From enrollment to the end of the observational period at 18 months or other endpoint
Cross-sectional differences in olfactory neuron transcriptomics	Difference between participants in different cohorts in olfactory neurons measured by Gateway in transcriptomic pathways associated with AD by human genetics.	Baseline
Change in clinical diagnosis	Measuring new clinical diagnoses of MCI and/or AD in participants without the diagnosis at the first visit	From enrollment to the end of the observational period at 18 months or final visit
Rate of change in MMSE	A secondary outcome is longitudinal changes from baseline in Mini-Mental State Examination, a 30-point evaluation where lower scores indicate cognitive worsening.	From enrollment to the end of the observational period at 18 months or final visit
Rate of change on RAVLT	A secondary outcome is longitudinal changes from baseline in Rey Auditory Verbal Learning Test, an assessment where lower scores indicate worsening episodic memory.	From enrollment to the end of the observational period at 18 months or final visit

Collaborators and Investigators

• Sponsor: Crownlands

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: May 14, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 28, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: genetics; biomarkers; longitudinal; alzheimer's; olfactory neurons
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: CLNDS-16530

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No