Detection of Alzheimer's Disease (AD)-Related Seeds for AD Diagnosis

Detection of Alzheimer's Disease (AD)-Related Seeds as Biomarkers for Accurate Diagnosis of AD（AD-seeds-detector）

The study will investigate the biomarkers of Aβ and Tau seeds in plasma detected by Alzheimer's disease (AD) related seeds quantitative detector (AD-seeds-detector), and their sensitivity and specificity in diagnosing AD, compared with those from age-matched cognitively normal controls, and those with other types of dementia.

To perform a high throughput analysis of the amount of Aβ and Tau seeds, the investigators have developed an AD-seeds-detector, in which a fluorescence microplate reader was combined with an oscillating mixer or water-bath-type ultrasonicator.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer's Disease

Detailed Description

Aβ and Tau seeds have the potential to serve as biomarkers for AD. The AD-seeds-detector could detect small quantities of Aβ and Tau seeds by taking advantage of their ability to nucleate and enhance aggregation, enabling a very high amplification of the signal. This study examines the effectiveness of using the AD-seeds-detector as a novel technique for discriminating AD from cognitively normal control and non-AD dementia by detecting small Aβ and Tau seeds in plasma.

This will be an observational study aiming at using the AD-seeds-detector to detect minute amounts of Aβ and Tau seeds in plasma as novel biomarkers with high sensitivity and specificity for the accurate diagnosis of AD. To achieve this goal, the investigators will conduct two studies using the AD-seeds-detector to detect the Aβ and Tau seeds in the plasma samples.

Study one:

A single-center cohort that consists of well-characterized AD patients (n=150), cognitively normal controls (n=100) and non-AD dementia patients (n=50).

Study two:

A multi-center cohort with well-characterized AD patients (n=400), cognitively normal controls (n=400) and non-AD dementia patients (n=400).

• Study Type: Observational
• Enrollment (Estimated): 1500

Contacts and Locations

• Study Contact: Name: Jianping Jia, Doctor; Phone Number: 8610-83199449; Email: jiajp@vip.126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Recruiting
      • Xuanwu Hospital of Capital Medical University
      • Contact: Jianping Jia, Doctor; Phone Number: 8610-83199449; Email: jiajp@vip.126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Study one: (1) AD patients (n=150); (2) cognitively normal controls (n=100); (3) non-AD dementia patients (n=50).

Study two: (1) AD patients (n=400); (2) cognitively normal controls (n=400); (3) non-AD dementia patients (n=400).

Description

Inclusion Criteria:

• Aged 55-75. Written informed consent obtained from participant or legal guardian prior to any study-related procedures. The diagnosis of AD is made using the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria. As for non-AD dementia, the McKeith criteria are used for DLB,the revised diagnostic criteria proposed by the International behavioral variant (bvFTD) Criteria Consortium for bvFTD,the Gorno-Tempini criteria for the semantic variant FTD or non-fluent aphasia, the Movement Disorder Society Task Force criteria for PDD, the vascular behavioral and cognitive disorders (Vas-Cog) criteria for VaD, the Armstrong's criteria for CBD, the CDC's diagnostic criteria for CJD, etc. In addition, normal cognition is supported by MMSE, CDR and other cognitive function scales.

Exclusion Criteria:

• Other medical or psychiatric illness. No one can serve as an informant. Refused to complete a cognitive test and provide biospecimen.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Alzheimer's disease; Criteria for AD according to the 2011 NIA-AA
Non-AD dementia; Frontotemporal dementia (FTD); or Parkinson's disease dementia (PDD); or dementia with Lewy bodies (DLB); or vascular dementia (VaD); or corticobasal degeneration (CBD); or dementia not otherwise specified.
Cognitively normal controls; Individuals with normal cognitive function

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The area under curve of the AD-seeds-detector for the accurate diagnosis of AD	The area under curve is used to show the ability of the AD-seeds-detector to diagnose AD. The value of area under curve is higher, then the ability of the AD-seeds-detector to diagnose AD is stronger.	two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The sensitivity	The sensitivity is used to show the ability of the AD-seeds-detector to diagnose AD patients, and is represented by true positive/ (true positive +false negative).	two years
The specificity	The specificity is used to show the ability of the AD-seeds-detector to avoid false AD patients and rule out AD patients, and is represented by true negative/ (false positive + true negative).	two years
The positive predictive value	The positive predictive value is used to show the ability of the AD-seeds-detector to correctly label AD patients who test positive, and is represented by true positive / (true positive + false positive)	two years
The negative predictive value	The negative predictive value is used to show the ability of the AD-seeds-detector to correctly label people who test negative, and is represented by true negative / (false negative + true negative)	two years
Cellular toxcity of Aβ seeds protein	Toxcity of Aβ seeds protein on cells	two years
Morphology and structure of Aβ	Comparison of Morphology and structure of beta-amyloid protein between difference groups	two years

Collaborators and Investigators

• Sponsor: Capital Medical University
• Collaborators: Xiangya Hospital of Central South University; Huashan Hospital; West China Hospital; First Affiliated Hospital Xi'an Jiaotong University; Shandong Provincial Hospital; Henan Provincial People's Hospital; Zhejiang Provincial People's Hospital; Beijing Geriatric Hospital; Kaifeng Central Hospital; The First Affiliated Hospital of Chongqing Medical Universty

Publications and helpful links

General Publications

• Jia J, Li T, Yang J, Chen B, Qin W, Wei C, Song Y, Wang Q, Li Y, Jia L. Detection of plasma Abeta seeding activity by a newly developed analyzer for diagnosis of Alzheimer's disease. Alzheimers Res Ther. 2022 Feb 2;14(1):21. doi: 10.1186/s13195-022-00964-2.

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: April 14, 2021
• First Submitted That Met QC Criteria: April 14, 2021
• First Posted (Actual): April 20, 2021

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Alzheimer's disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: AD-seeds-detector

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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