Blood Tests for Alzheimer's Disease: Can Plasma Biomarkers Diagnose and Predict Disease Progression

NCT07717567 | Recruiting

• 1 other identifier: BLAD
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief Summary

BLAD is a prospective, monocentric, observational epidemiological study with an additional procedure (annual blood draw) evaluating the diagnostic and prognostic performance of plasma biomarkers for Alzheimer's disease (AD) in a large cohort of patients attending the Cognitive Disorders and Dementia Center (CDCD) at IRCCS San Raffaele Hospital, Milan, Italy. 2000 patients will be enrolled and followed annually for 5 years. A validation sub-study (150 patients) will compare plasma biomarkers against CSF biomarkers as the gold standard. The study aims to establish plasma biomarkers as a less invasive and more cost-effective alternative to CSF analysis and amyloid-PET for the diagnosis and prognosis of AD.

Conditions

Alzheimer Disease; Mild Cognitive Impairment; Subjective Cognitive Decline; Dementia; Cognitive Impairment

Keywords

Alzheimer's disease; Plasma biomarkers; pTau-181; Abeta42; Abeta40; NfL; GFAP; sTREM2; ApoE; Mild Cognitive Impairment; Subjective Cognitive Decline; Dementia; Blood biomarkers; Diagnostic accuracy; Prognosis

Outcome Measures

Primary Outcomes (1)

• Time to progression to all-cause dementia in MCI patients (primary prognostic endpoint)

  Time to clinical progression to all-cause dementia in patients with Mild Cognitive Impairment (MCI) at baseline, assessed using multivariable Cox proportional hazards models. For each plasma biomarker, patients are divided into two groups (above/below the median) and compared using the log-rank test (cause-specific hazard). The study has greater than 95% power to detect a Hazard Ratio of 2 and approximately 75-80% power for HR of 1.5.

  Annually from baseline up to 5 years

Secondary Outcomes (9)

• Change in MMSE score over time

  Annually from baseline up to 5 years

• Conversion from MCI to Alzheimer's disease dementia

  Annually from baseline up to 5 years

• Longitudinal change in plasma Abeta42/Abeta40 ratio

  Annually from baseline up to 5 years

• Longitudinal change in plasma pTau-181 levels

  Annually from baseline up to 5 years

• Longitudinal change in plasma NfL levels

  Annually from baseline up to 5 years

Other Outcomes (13)

• Diagnostic accuracy of plasma Abeta42/Abeta40 ratio vs CSF gold standard (sub-study)

  Baseline (at time of lumbar puncture, within 6 months of blood draw)

• Diagnostic accuracy of plasma pTau-181 vs CSF gold standard (sub-study)

  Baseline (at time of lumbar puncture, within 6 months of blood draw)

• Diagnostic accuracy of plasma NfL vs CSF gold standard (sub-study)

  Baseline (at time of lumbar puncture, within 6 months of blood draw)

Study Arms (2)

Main Study Cohort

2000 adult patients attending the Cognitive Disorders and Dementia Center (CDCD) at IRCCS San Raffaele Hospital with subjective or objective cognitive complaints of progressive and suspected neurodegenerative nature. All patients undergo annual blood sampling for 5 years in addition to standard clinical follow-up.

Procedure: Annual blood draw for plasma biomarker measurement

Validation Sub-study Cohort

150 patients from the main cohort who undergo lumbar puncture as part of their routine diagnostic workup and have CSF biomarkers for Alzheimer's disease available within 6 months of blood draw. Only those with CSF biomarkers confirming a biological diagnosis of Alzheimer's disease continue longitudinal follow-up in the sub-study.

Procedure: Annual blood draw for plasma biomarker measurement

Interventions

Annual blood draw for plasma biomarker measurement PROCEDURE

A blood sample is collected once per year for 5 years (additional procedure beyond standard clinical care) for measurement of plasma biomarkers including: Abeta40, Abeta42, Abeta42/Abeta40 ratio, pTau-181, NfL, ApoE, ApoE4, GFAP, sTREM2, and other plasma neurodegeneration biomarkers. Blood draw is a routine clinical procedure with no specific contraindications. The only possible side effect is local hematoma at the puncture site. Plasma biomarker measurement is performed using a CE-marked medical device (Fujirebio, provided on free loan). Results do not modify the patient's standard diagnostic and therapeutic pathway.

Main Study Cohort; Validation Sub-study Cohort

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients attending the Cognitive Disorders and Dementia Center (CDCD) at IRCCS San Raffaele Hospital, Milan, Italy, presenting with subjective or objective cognitive complaints of progressive and suspected neurodegenerative nature.

You may qualify if:

• Age greater than or equal to 40 years (patients of childbearing age are admitted).
• Subjective or objective cognitive complaints, progressive in nature and of suspected neurodegenerative origin.
• Mini-Mental State Examination (MMSE) score greater than or equal to 18.
• Availability of CSF biomarkers for Alzheimer's disease within 6 months of the blood draw.

You may not qualify if:

• Secondary forms of cognitive impairment based on medical history, neurological examination, and neuroimaging findings.
• Pregnancy or breastfeeding.
• Rapidly progressive cognitive decline occurring over weeks or months, typically indicative of prion disease, neoplasia, or metabolic disorders.
• Subjects who require a legal guardian or tutor.
• Secondary forms of cognitive impairment based on medical history, neurological examination, and neuroimaging findings.
• Pregnancy.
• Rapidly progressive cognitive decline occurring over weeks or months, typically indicative of prion disease, neoplasia, or metabolic disorders.
• Subjects who are unable to give informed consent and require a legal guardian or tutor.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

IRCCS Ospedale San Raffaele - Cognitive Disorders and Dementia Center (CDCD)

Milan, Milano, 20132, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples (plasma) collected annually for 5 years for measurement of plasma biomarkers (Abeta40, Abeta42, pTau-181, NfL, ApoE, ApoE4, GFAP, sTREM2, and other plasma neurodegeneration biomarkers). Residual samples stored at the INSPE Experimental Neuropathology Unit biobank for a maximum of 15 years after collection.

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Dementia

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Study Officials

• Massimo Filippi, Prof, MD

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Federica Agosta, MD

CONTACT

0226433051; agosta.federica@hsr.it

Giuseppe Magnani, MD

CONTACT

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof, MD

Study Record Dates

• First Submitted: July 16, 2026
• First Posted: July 21, 2026
• Study Start: September 12, 2023
• Primary Completion (Estimated): June 1, 2032
• Study Completion (Estimated): June 1, 2032
• Last Updated: July 21, 2026

Record last verified: 2026-07

Locations

IT (1)