Alzheimer DiseaseBLADNCT07717567
Blood Tests for Alzheimer's Disease: Can Plasma Biomarkers Diagnose and Predict Disease Progression
An observational study of Alzheimer Disease and Mild Cognitive Impairment, run by IRCCS San Raffaele at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Alzheimer Disease, Mild Cognitive Impairment, Subjective Cognitive Decline
- What is being tested?
- Annual blood draw for plasma biomarker measurement
- Type of treatment
- Surgery or procedure
- How many people
- 2,000 participants
- Where
- 1 siteItaly
- Study dates
- 12 Sep 2023to 1 Jun 2032
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
- Additional inclusion criterion for the validation sub-study:
- Availability of CSF biomarkers for Alzheimer's disease within 6 months of the blood draw.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Giuseppe Magnani, MD contact
Italy1 site, 1 recruiting
- Recruiting
IRCCS Ospedale San Raffaele - Cognitive Disorders and Dementia Center (CDCD)
Milan, Milano, 20132
Federica Agosta, MD, 0226433051, agosta.federica@hsr.it
Giuseppe Magnani, MD
About this study
Official title: The Diagnostic and Prognostic Role of Plasma Biomarkers in Alzheimer's Disease
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.
Read the detailed description
In light of the possible advent of disease-modifying drugs for Alzheimer's disease (AD), reliable biomarkers have been developed in recent years to define the presence of AD pathology at the brain level. The current biological gold standards are cerebrospinal fluid (CSF) biomarkers (CSF-Abeta40, CSF-Abeta42, CSF-pTau, CSF-NfL) and amyloid-PET. Both methods have excellent diagnostic properties but are costly and invasive, limiting their use outside of highly specialized centers.
Plasma biomarkers (plasma-Abeta40, plasma-Abeta42, plasma-pTau-181, plasma-NfL, plasma-ApoE, plasma-ApoE4, plasma-GFAP, plasma-sTREM2, and other plasma neurodegeneration biomarkers) represent a potentially less invasive and more economically accessible alternative. Recent studies have shown that plasma biomarkers can differentiate AD from other neurodegenerative disorders with accuracy comparable to CSF and PET, detect AD pathology in MCI patients, and predict future development of AD dementia in patients with SCD or MCI. However, more research is needed before their widespread use in clinical practice.
The BLAD study is designed as a monocentric, prospective, observational epidemiological study with an additional procedure (annual blood draw for 5 years) and a diagnostic accuracy sub-study (not device-based).
Patients will be recruited among those attending the Cognitive Disorders and Dementia Center (CDCD) at IRCCS San Raffaele Hospital during routine clinical practice. All enrolled patients will undergo annual blood sampling for 5 years in addition to standard clinical assessments.
A sub-population of 150 patients who undergo lumbar puncture as part of their routine diagnostic workup will enter the validation sub-study. Only those whose CSF biomarkers confirm a biological diagnosis of Alzheimer's disease will continue follow-up; others will exit the sub-study.
The equipment for plasma biomarker measurement (CE-marked medical device) and laboratory kits will be provided on free loan by Fujirebio. No clinical or laboratory data will be shared with Fujirebio.
Statistical analyses will include: log-rank test to compare time to AD development between groups above and below the biomarker threshold; linear stepwise regression models, linear mixed-effects models, and multivariable Cox models to assess the prognostic value of plasma biomarkers; longitudinal generalized linear models for repeated measures or Wilcoxon test to assess biomarker dynamics over time. For the validation sub-study, ROC curve analysis will be performed to assess accuracy, sensitivity, and specificity of plasma biomarkers against CSF gold standard.
- Conditions
- Alzheimer Disease, Mild Cognitive Impairment, Subjective Cognitive Decline, Dementia, Cognitive Impairment
- Being tested
- Annual blood draw for plasma biomarker measurement
- 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
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Annual blood draw for plasma biomarker measurementProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Annual blood draw for plasma biomarker measurement |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Annually from baseline up to 5 years
Secondary outcomes (9)
Change in MMSE score over time
Change over time in Mini-Mental State Examination (MMSE) score as a measure of cognitive progression. A decrease of 5 or more points is considered clinically significant progression of cognitive impairment due to AD.
Measured: Annually from baseline up to 5 years
Conversion from MCI to Alzheimer's disease dementia
Rate of clinical conversion from Mild Cognitive Impairment (MCI) to Alzheimer's disease dementia over the 5-year follow-up period, assessed at each annual visit.
Measured: Annually from baseline up to 5 years
Longitudinal change in plasma Abeta42/Abeta40 ratio
Change over time in the plasma Abeta42/Abeta40 ratio, assessed using longitudinal generalized linear models for repeated measures or Wilcoxon test.
Measured: Annually from baseline up to 5 years
Longitudinal change in plasma pTau-181 levels
Change over time in plasma phosphorylated tau 181 (pTau-181) levels, assessed using longitudinal generalized linear models for repeated measures or Wilcoxon test.
Measured: Annually from baseline up to 5 years
Longitudinal change in plasma NfL levels
Change over time in plasma neurofilament light chain (NfL) levels, assessed using longitudinal generalized linear models for repeated measures or Wilcoxon test.
Measured: Annually from baseline up to 5 years
Longitudinal change in plasma GFAP levels
Change over time in plasma Glial Fibrillary Acidic Protein (GFAP) levels, assessed using longitudinal generalized linear models for repeated measures or Wilcoxon test.
Measured: Annually from baseline up to 5 years
Longitudinal change in plasma sTREM2 levels
Change over time in plasma soluble Triggering Receptor Expressed on Myeloid cells 2 (sTREM2) levels, assessed using longitudinal generalized linear models for repeated measures or Wilcoxon test.
Measured: Annually from baseline up to 5 years
Longitudinal change in plasma Abeta40 levels
Change over time in plasma beta-amyloid 40 (Abeta40) levels, assessed using longitudinal generalized linear models for repeated measures or Wilcoxon test.
Measured: Annually from baseline up to 5 years
Longitudinal change in plasma Abeta42 levels
Change over time in plasma beta-amyloid 42 (Abeta42) levels, assessed using longitudinal generalized linear models for repeated measures or Wilcoxon test.
Measured: Annually from baseline up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2026
- Study start12 Sep 2023
- Primary completion1 Jun 2032 (estimated)
- Study completion1 Jun 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Massimo Filippi, IRCCS San Raffaele
- Investigators
- Massimo Filippi, Prof, MD, Principal investigator, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07717567
- Sponsor's protocol ID
- BLAD
- Acronym
- BLAD
- Status last verified
- Jul 2026
- First submitted
- 16 Jul 2026
- Last updated
- 21 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Diagnostic and Prognostic Role of Plasma Biomarkers in Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT07717567
- Acronym / sponsor ID
- BLAD / BLAD
- 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
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- 12 Sep 2023 (actual)
- Primary completion
- 1 Jun 2032 (estimated)
- Study completion
- 1 Jun 2032 (estimated)
- First posted
- 21 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In light of the possible advent of disease-modifying drugs for Alzheimer's disease (AD), reliable biomarkers have been developed in recent years to define the presence of AD pathology at the brain level. The current biological gold standards are cerebrospinal fluid (CSF) biomarkers (CSF-Abeta40, CSF-Abeta42, CSF-pTau, CSF-NfL) and amyloid-PET. Both methods have excellent diagnostic properties but are costly and invasive, limiting their use outside of highly specialized centers.
Plasma biomarkers (plasma-Abeta40, plasma-Abeta42, plasma-pTau-181, plasma-NfL, plasma-ApoE, plasma-ApoE4, plasma-GFAP, plasma-sTREM2, and other plasma neurodegeneration biomarkers) represent a potentially less invasive and more economically accessible alternative. Recent studies have shown that plasma biomarkers can differentiate AD from other neurodegenerative disorders with accuracy comparable to CSF and PET, detect AD pathology in MCI patients, and predict future development of AD dementia in patients with SCD or MCI. However, more research is needed before their widespread use in clinical practice.
The BLAD study is designed as a monocentric, prospective, observational epidemiological study with an additional procedure (annual blood draw for 5 years) and a diagnostic accuracy sub-study (not device-based).
Patients will be recruited among those attending the Cognitive Disorders and Dementia Center (CDCD) at IRCCS San Raffaele Hospital during routine clinical practice. All enrolled patients will undergo annual blood sampling for 5 years in addition to standard clinical assessments.
A sub-population of 150 patients who undergo lumbar puncture as part of their routine diagnostic workup will enter the validation sub-study. Only those whose CSF biomarkers confirm a biological diagnosis of Alzheimer's disease will continue follow-up; others will exit the sub-study.
The equipment for plasma biomarker measurement (CE-marked medical device) and laboratory kits will be provided on free loan by Fujirebio. No clinical or laboratory data will be shared with Fujirebio.
Statistical analyses will include: log-rank test to compare time to AD development between groups above and below the biomarker threshold; linear stepwise regression models, linear mixed-effects models, and multivariable Cox models to assess the prognostic value of plasma biomarkers; longitudinal generalized linear models for repeated measures or Wilcoxon test to assess biomarker dynamics over time. For the validation sub-study, ROC curve analysis will be performed to assess accuracy, sensitivity, and specificity of plasma biomarkers against CSF gold standard.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Main Study Cohort | – | Procedure: Annual blood draw for plasma biomarker measurement2000 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. |
| Validation Sub-study Cohort | – | Procedure: Annual blood draw for plasma biomarker measurement150 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. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Annual blood draw for plasma biomarker measurementA 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. | Procedure or surgery | Main Study Cohort, Validation Sub-study Cohort |
Primary outcome
Time to progression to all-cause dementia in MCI patients (primary prognostic endpoint)
Time frame: Annually from baseline up to 5 years
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.
9 secondary outcomes
Change in MMSE score over time
Time frame: Annually from baseline up to 5 years
Conversion from MCI to Alzheimer's disease dementia
Time frame: Annually from baseline up to 5 years
Longitudinal change in plasma Abeta42/Abeta40 ratio
Time frame: Annually from baseline up to 5 years
Longitudinal change in plasma pTau-181 levels
Time frame: Annually from baseline up to 5 years
Longitudinal change in plasma NfL levels
Time frame: Annually from baseline up to 5 years
Longitudinal change in plasma GFAP levels
Time frame: Annually from baseline up to 5 years
Longitudinal change in plasma sTREM2 levels
Time frame: Annually from baseline up to 5 years
Longitudinal change in plasma Abeta40 levels
Time frame: Annually from baseline up to 5 years
Longitudinal change in plasma Abeta42 levels
Time frame: Annually from baseline up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Giuseppe Magnani, MD contact
Massimo Filippi, Prof, MD principal investigator
IRCCS San Raffaele
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alzheimer Disease and Mild Cognitive Impairment, run by IRCCS San Raffaele at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Federica Agosta, MD (0226433051, agosta.federica@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to progression to all-cause dementia in MCI patients (primary prognostic endpoint) (time frame: Annually from baseline up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.