The CORCOBIA study: Cut-off points of Alzheimer’s disease CSF biomarkers in a clinical cohort

Introduction: Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences. Methods:In the BIODEGMAR study, 197 participants presenting with cognitive complaints were classified into an Alzheimer's disease (AD) or a non-AD cerebrospinal fluid (CSF) profile group, according to their amyloid beta 42/ phosphorylated tau (Aβ42/p-tau) ratio. We performed a head-to-head comparison of nine plasma and nine CSF tau immunoassays and determined their accuracy to discriminate abnormal CSF Aβ42/p-tau ratio.Results: All studied plasma tau biomarkers were significantly higher in the AD CSF profile group compared to the non-AD CSF profile group and significantly discriminated abnormal CSF Aβ42/p-tau ratio. For plasma p-tau biomarkers, the higher discrimination accuracy was shown by Janssen p-tau217 (r = 0.76; area under the curve[AUC] = 0.96), ADx p-tau181 (r = 0.73; AUC = 0.94), and Lilly p-tau217 (r = 0.73; AUC = 0.94).Discussion: Several plasma p-tau biomarkers can be used in a specialized memory clinic as a stand-alone biomarker to detect biologically-defined AD.

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Plasma and CSF biomarkers in a memory clinic: Head‐to‐head comparison of phosphorylated tau immunoassays

Ashton

Puig‐Pijoan

Milà‐Alomà

et al. 2022

“…For TRIAD, CSF Aβ 42/40 and p‐tau181 cutoffs (for Aβ− and tau‐positivity, respectively) were defined based on young CU individuals [±2.5 standard deviations (SD)] 19 . For BIODEGMAR, individuals were classified as Aβ‐negative using CSF Aβ 42/40 following a previously calculated cutoff 20 …”

Section: Methodsmentioning

confidence: 99%

Blood‐brain barrier integrity impacts the use of plasma amyloid‐β as a proxy of brain amyloid‐β pathology

Bellaver

Puig‐Pijoan

Ferrari‐Souza

et al. 2023

INTRODUCTIONAmyloid‐β (Aβ) and tau can be quantified in blood. However, biological factors can influence the levels of brain‐derived proteins in the blood. The blood‐brain barrier (BBB) regulates protein transport between cerebrospinal fluid (CSF) and blood. BBB altered permeability might affect the relationship between brain and blood biomarkers.METHODSWe assessed 224 participants in research (TRIAD, n = 96) and clinical (BIODEGMAR, n = 128) cohorts with plasma and CSF/positron emission tomography Aβ, p‐tau, and albumin measures.RESULTSPlasma Aβ42/40 better identified CSF Aβ42/40 and Aβ‐PET positivity in individuals with high BBB permeability. An interaction between plasma Aβ42/40 and BBB permeability on CSF Aβ42/40 was observed. Voxel‐wise models estimated that the association of positron emission tomography (PET), with plasma Aβ was most affected by BBB permeability in AD‐related brain regions. BBB permeability did not significantly impact the relationship between brain and plasma p‐tau levels.DISCUSSIONThese findings suggest that BBB integrity may influence the performance of plasma Aβ, but not p‐tau, biomarkers in research and clinical settings.Highlights BBB permeability affects the association between brain and plasma Aβ levels. BBB integrity does not affect the association between brain and plasma p‐tau levels. Plasma Aβ was most affected by BBB permeability in AD‐related brain regions. BBB permeability increases with age but not according to cognitive status.

“…We conducted a prospective observational study of patients consecutively included in the BIODEGMAR cohort 21…”

Section: Participants and Study Designmentioning

confidence: 99%

Risk of cognitive decline progression is associated to increased blood‐brain‐barrier permeability: A longitudinal study in a memory unit clinical cohort

Puig‐Pijoan,

Jimenez‐Balado,

Fernández‐Lebrero

et al. 2023

INTRODUCTIONThis study examined the relationship between blood‐brain‐barrier permeability (BBBp), measured by cerebrospinal fluid/serum albumin ratio (QAlb), and cognitive decline progression in a clinical cohort.METHODSThis prospective observational study included 334 participants from the BIODEGMAR cohort. Cognitive decline progression was defined as an increase in Global Deterioration Scale and/or Clinical Dementia Rating scores. Associations between BBBp, demographics, and clinical factors were explored.RESULTSMale sex, diabetes mellitus, and cerebrovascular burden were associated with increased log‐QAlb. Vascular cognitive impairment patients had the highest log‐QAlb levels. Among the 273 participants with valid follow‐up data, 154 (56.4%) showed cognitive decline progression. An 8% increase in the hazard of clinical worsening was observed for each 10% increase in log‐QAlb.DISCUSSIONThese results suggest that increased BBBp in individuals with cognitive decline may contribute to clinical worsening, pointing to potential targeted therapies. QAlb could be a useful biomarker for identifying patients with a worse prognosis.