Clinical Evaluation of Blood-Based Assays for Rapid Detection of Aβ Pathology in Alzheimer's Disease

Launched by ANHUI PROVINCIAL HOSPITAL · Mar 17, 2025

Keywords

ClinConnect Summary

CLEAR-AD is a China-wide study that looks at whether simple blood tests can tell us if someone has brain changes linked to Alzheimer’s disease, as well as how well these tests work compared with the standard brain scan (amyloid PET). Researchers are comparing several blood markers (Aβ40, Aβ42, t-tau, and p-tau181/217) using different testing methods to see if they can accurately predict amyloid buildup in the brain. The study plans to enroll about 400 people across 10 centers, including people with normal thinking, people with mild cognitive impairment, and people with dementia. All participants have an amyloid PET scan and give blood samples around the same time, with the blood tested in a central, blinded lab.

People eligible to join are adults aged 45 to 85 who can provide informed consent. They can be cognitively normal, have mild cognitive impairment (whether amyloid PET is positive or negative), or have dementia (also categorized by amyloid status). Requirements include having an amyloid PET within the past three months, undergoing MRI and cognitive tests, and providing blood samples (frozen plasma or a small amount of whole blood) within three months of the PET scan. Exclusions include certain mental or CNS illnesses, severe liver or kidney problems, major substance abuse, or prior anti-amyloid treatments unless part of a placebo group. The study is observational and not testing a drug, and results are intended to help determine which blood tests might soon support faster, easier screening for Alzheimer’s pathology. Enrollment is ongoing, with primary completion expected around mid-2025.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• Patient Group (including MCI, AD, and Non-AD Dementia):
• • 1. Clear complaints of cognitive impairment, with MCI and AD diagnoses meeting the NIA-AA 2011 diagnostic criteria. Non-AD dementia is defined as patients with cognitive decline diagnosed with dementia due to other reasons (including but not limited to FTD, DLB, VD, PDD, etc.).
• • 2. Able to provide informed consent or have a legal guardian who can sign the consent form.
• • 3. Completed a full set of cognitive assessments, including MMSE and CDR.
• • 4. Able to provide a history of chronic diseases, including cardiovascular diseases, diabetes, etc., and medication history.
• • 5. Have undergone amyloid protein PET scans that meet the quality requirements of this study (tracers PiB, AV1, or AV45), and can provide original imaging data for quantitative analysis without conflict.
• • 6. Can provide frozen plasma from a biobank collected after January 1, 2024, with a time interval of ≤3 months from the amyloid protein PET scan. If no frozen plasma is available, willing to provide an additional 5ml of whole blood for biomarker testing in this project. The process of blood collection, plasma separation, storage, and transportation meets the quality requirements of this study (see blood testing SOP).
• • 7. Have 3D-T1 structural MRI images taken within 3 months before and after the amyloid protein PET scan and can provide original imaging data without conflict.
• Normal Control Group:
• • 1. Subjects with a CDR score of 0 and who have undergone amyloid protein PET scans that are negative.
• • 2. Able to provide informed consent.
• • 3. Completed a full set of cognitive assessments, including MMSE and CDR.
• • 4. Able to provide a history of chronic diseases, including cardiovascular diseases, diabetes, etc., and medication history.
• • 5. Have undergone amyloid protein PET scans that meet the quality requirements of this study (tracers PiB, AV1, or AV45), and can provide original imaging data for quantitative analysis without conflict.
• • 6. Can provide frozen plasma from a biobank collected after January 1, 2024, with a time interval of ≤3 months from the amyloid protein PET scan. If no frozen plasma is available, willing to provide an additional 5ml of whole blood for biomarker testing in this project. The process of blood collection, plasma separation, storage, and transportation meets the quality requirements of this study (see blood testing SOP).
• • 7. Have 3D-T1 structural MRI images taken within 3 months before and after the amyloid protein PET scan and can provide original imaging data without conflict.
• Exclusion Criteria:
• • 1. History of Mental Illness:\*\* Depression (Geriatric Depression Scale \[GDS\] \> 7 points or Hamilton Depression Rating Scale \[17-item version\] \> 7 points);
• • 2. History of Central Nervous System Diseases:\*\* Including infections, epilepsy, multiple sclerosis, toxic metabolic diseases, familial hereditary diseases, neurotumors, etc.;
• • 3. Severe Stroke Sequelae:\*\* mRS \> 3 points or a documented history of stroke sequelae;
• • 4. Severe Liver and Kidney Dysfunction at Diagnosis:\*\* ALT ≥ 5 times the upper limit of normal, or estimated glomerular filtration rate (eGFR) \< 30 ml·min-¹·(1.73 m²)-¹, or patients requiring renal replacement therapy;
• • 5. History of Drug Abuse and Severe Alcoholism;\*\*
• • 6. Prior Use of Anti-Aβ or Other Disease-Modifying Treatments,\*\* unless there is clear evidence of a placebo group;
• • 7. Severe Hyperlipidemia:\*\* Triglycerides ≥ 5.6 mmol/L or visible chylomicron changes in plasma.