Immunohistochemical Study of Neurodegenerative Diseases

Immunohistochemical Study of Peripheral Blood Mononuclear Cells in Sporadic Alzheimer's Disease and Dementia With Lewy Body

The subject uses cytof to analyze PBMC of sporadic AD and DLB, which is used to reveal the differences in immune characteristics of the two diseases at the single-cell level, build immune models for specific diseases, and define these two neurodegenerative diseases with high precision from the level of molecular immunity. To provide basis for further study of the immunohistochemical differences between the two diseases, and provide objective support for clinical diagnosis and differential diagnosis.

Study Overview

• Status: Recruiting
• Conditions: Neurodegenerative Diseases; Alzheimer Disease; Lewy Body Disease
• Intervention / Treatment: Biological: Detection of cytof in peripheral PBMC; Drug: Donepezil for patients with AD and DLB

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hu ShaoHua; Phone Number: 086-13957162903; Email: dorhushaohua@zju.edu.cn
• Study Contact Backup: Name: Qiu CongLong; Phone Number: 086-15258339029; Email: qcl198731@126.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Department of Psychiatry, First Affiliated Hospital of Zhejiang University
      • Contact: Hu ShaoHua; Phone Number: 13957162903; Email: dorhushaohua@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. AD inclusion criteria:

   a.Clinical diagnosis of Alzheimer's Disease

2. DLB inclusion criteria:

   1. Clinical diagnosis of Dementia with Lewy bodies

Exclusion Criteria:

1. Infectious diseases
2. autoimmune disease
3. heart failure
4. chronic obstructive pulmonary disease (COPD)
5. cancer
6. renal failure
7. recently major surgery
8. alcohol and / or drug abuse
9. disturbance of consciousness
10. clinical diagnosis of major depression disorder
11. clinical diagnosis of Anxiety disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AD group; 20 subjects who met the diagnostic criteria and exclusion criteria of AD were included in the discovery cohort.	Biological: Detection of cytof in peripheral PBMC; Each subject needs to take 5ml of peripheral venous blood to extract PBMC cells, and then conduct cytof detection. This is a mass spectrometry flow cytometry method based on single cell level. It has the ability to analyze all immune cells with high resolution.; Drug: Donepezil for patients with AD and DLB; The subjects in AD and DLB groups were given donepezil at an initial dose of 5mg and then increased to 10mg one month later. Lasting for 1 year.
Experimental: DLB group; Of the 30 subjects who met the DLB diagnostic criteria and exclusion criteria, 20 were included in the discovery cohort and 10 in the validation cohort.	Biological: Detection of cytof in peripheral PBMC; Each subject needs to take 5ml of peripheral venous blood to extract PBMC cells, and then conduct cytof detection. This is a mass spectrometry flow cytometry method based on single cell level. It has the ability to analyze all immune cells with high resolution.; Drug: Donepezil for patients with AD and DLB; The subjects in AD and DLB groups were given donepezil at an initial dose of 5mg and then increased to 10mg one month later. Lasting for 1 year.
Experimental: Healthy control group; Among the 30 subjects who met the diagnostic and exclusion criteria of the healthy control group, 20 were included in the discovery cohort and 10 in the validation cohort.	Biological: Detection of cytof in peripheral PBMC; Each subject needs to take 5ml of peripheral venous blood to extract PBMC cells, and then conduct cytof detection. This is a mass spectrometry flow cytometry method based on single cell level. It has the ability to analyze all immune cells with high resolution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunerepertorie	The immune cells were drawn into immunoreceptor by mass cytometry (cytof) technology. Immunerepertorie is used for the classification of immune cells. According to the proportion of various immune cell subtypes and biomarkers in all cells, it is used to find the difference between immune cell subtypes and biomarkers in different diseases. Scoring frame: 0-1. The higher the score, the greater the proportion of this subtype or biomarker.	1 year
immunological Elastic-Net (iEN) model	The immunological Elastic-Net (iEN), which incorporates immunological knowledge directly into the predictive models. The ROC curve output by the model is plotted with specificity as the abscissa and sensitivity as the ordinate, and the AUC (area under the curve) value is calculated. The AUC value was used to evaluate the authenticity of the IEN model. Score frame: 0.5-1. A higher value indicates that the model is closer to the real situation.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini-mental State Examination（MMSE）	MMSE was used to evaluate the degree of intellectual status and cognitive impairment. Score frame: 0 ~ 30. The lower the score, the more severe the cognitive impairment.	1 year

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Investigators: Study Chair: Li YouMing, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 30, 2023

Study Registration Dates

• First Submitted: August 9, 2022
• First Submitted That Met QC Criteria: August 25, 2022
• First Posted (Actual): August 26, 2022

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: September 13, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Dementia; Tauopathies; Alzheimer Disease; Neurodegenerative Diseases; Lewy Body Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: IIT20220213B-R1

Drug and device information, study documents

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