Clinical trial NCT04850053: Detection of Alzheimer's Disease (AD)-Related Seeds for AD Diagnosis
Official title: Detection of Alzheimer's Disease (AD)-Related Seeds as Biomarkers for Accurate Diagnosis of AD（AD-seeds-detector）
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Alzheimer's Disease
Keywords: Alzheimer's disease
Lead sponsor: Capital Medical University
Sponsor class: OTHER
Collaborators: name: Shandong Provincial Hospital
name: Xiangya Hospital of Central South University
name: Zhejiang Provincial People's Hospital
name: Beijing Geriatric Hospital
name: Kaifeng Central Hospital
name: The First Affiliated Hospital of Chongqing Medical Universty
name: Huashan Hospital
name: First Affiliated Hospital Xi'an Jiaotong University
name: West China Hospital
name: Henan Provincial People's Hospital
First posted: 2021-04-20
Enrollment: 1500
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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).

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: The area under curve of the AD-seeds-detector for the accurate diagnosis of AD
timeFrame: two years
Secondary outcomes:
measure: The sensitivity
timeFrame: two years
measure: The specificity
timeFrame: two years
measure: The positive predictive value
timeFrame: two years
measure: The negative predictive value
timeFrame: two years
measure: Cellular toxcity of Aβ seeds protein
timeFrame: two years
measure: Morphology and structure of Aβ
timeFrame: two years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital of Capital Medical University
state: Beijing
Study officials:
References:
citation: 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.