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

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.

• Change in MMSE score over time [Срок оценки: Annually from baseline up to 5 years]
• Conversion from MCI to Alzheimer's disease dementia [Срок оценки: Annually from baseline up to 5 years]
• Longitudinal change in plasma Abeta42/Abeta40 ratio [Срок оценки: Annually from baseline up to 5 years]
• Longitudinal change in plasma pTau-181 levels [Срок оценки: Annually from baseline up to 5 years]
• Longitudinal change in plasma NfL levels [Срок оценки: Annually from baseline up to 5 years]
• Longitudinal change in plasma GFAP levels [Срок оценки: Annually from baseline up to 5 years]
• Longitudinal change in plasma sTREM2 levels [Срок оценки: Annually from baseline up to 5 years]
• Longitudinal change in plasma Abeta40 levels [Срок оценки: Annually from baseline up to 5 years]
• Longitudinal change in plasma Abeta42 levels [Срок оценки: Annually from baseline up to 5 years]