Age-specific control and Alzheimers disease reference curves and z-scores for glial fibrillary acidic protein in blood DOI Creative Commons
Steffen Halbgebauer, Badrieh Fazeli, Veronika Klose

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

Abstract Background Serum glial fibrillary acidic protein (GFAP) is a biomarker for astrocytic injury and astrogliosis. Concentrations are elevated in numerous neurological disorders, including pronounced increase Alzheimer’s disease (AD). However, GFAP levels the serum also with age. Consequently, integration of into clinical routine their interpretation demands age-adjusted reference values. Methods from 1273 subjects (952 non-inflammatory non-neurodegenerative controls 321 AD) were analyzed using microfluidic Ella system. Age-dependent values calculated by additive quantile regression analysis. Percentiles z-scores employed presentation as function Results All patients within AD continuum exhibited statistically comparison to control cohort (p<0.0001). This remained case when newly generated age-corrected applied In cohort, non-linear elevation increasing age was observed (Spearman correlation coefficient (r) 0.62, 95%CI 0.58-0.66, p<0.0001). contrast, more linear (0.16, 0.05-0.26, p=0.004). cut-offs different groups. The areas under curve (AUC 0.97) demonstrated excellent diagnostic test performance early onset group. effect less marked elderly 0.72). Conclusions Our novel enable practice, moving group individual level. They support both intra- interindividual single diseases pathology, an accurate discrimination disease.

Language: Английский

Clinical Utility of an Alzheimer’s Disease Blood Test Among Cognitively Impaired Patients: Results from the Quality Improvement PrecivityAD2 (QUIP II) Clinician Survey Study DOI Creative Commons
Mark Monane, Demetrius M. Maraganore,

Robert G. Carlile

et al.

Diagnostics, Journal Year: 2025, Volume and Issue: 15(2), P. 167 - 167

Published: Jan. 13, 2025

Objective: The objective of this study was to assess clinical decision-making associated with the use a multi-analyte blood biomarker (BBM) test among patients presenting signs or symptoms mild cognitive impairment dementia. Methods: Quality Improvement PrecivityAD2 (QUIP II) Clinician Survey (NCT06025877) evaluated utility PrecivityAD2™ in prospective, single cohort 203 Alzheimer’s disease (AD) other causes decline across 12 memory specialists. (C2N Diagnostics, St. Louis, MO) combines plasma Aβ42/Aβ40 ratio and p-tau217/np-tau217 (%p-tau217) measurements statistical algorithm yield an Amyloid Probability Score 2 (APS2) that informs on likelihood brain amyloid plaques. After receiving BBM results, clinicians completed surveys management strategies for each patient. Results: Patients had median age 74, 53% were female, 28% traditionally under-represented Black, Hispanic, Asian groups. composite primary endpoint, defined as change AD diagnostic certainty, drug therapy, additional evaluation pre- post-BBM testing, 75% (p < 0.0001 versus pre-specified threshold 20% clinically meaningful change). Anti-AD medication orders decreased negative APS2 increased positive 0.0001). Additional testing Conclusions: This can help specialists guide anti-AD therapies well rule out allow considerations.

Language: Английский

Citations

0
Biomarker-guided decision making in clinical drug development for neurodegenerative disorders DOI
Jeffrey L. Cummings, Charlotte E. Teunissen, Brian Fiske

et al.

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Language: Английский

Citations

0
Defining benefit: Clinically and biologically meaningful outcomes in the next‐generation Alzheimer's disease clinical care pathway DOI Creative Commons

Aya Elhage,

Sharon Cohen,

Jeffrey L. Cummings

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 19, 2024

To understand the potential benefits of emerging Alzheimer's disease (AD) therapies within and beyond clinical trial settings, there is a need to advance current outcome measurements into meaningful information relevant all stakeholders. The relationship between impact on biology clinically measurable outcomes in cognition, function, behavior must be considered when defining benefit early AD therapies. In this review, we discuss: (1) lack consideration for biomarkers concept meaningfulness AD; (2) gold standards determining minimal biologically important differences (MBCIDs) trials; (3) how treatment disease-modifying treatments are cumulative increase over time; (4) different concepts among key This review utilizes future biological framework aims further integrate expand parameters toward precision medicine framework. HIGHLIGHTS: Definition from varies across stage stakeholder perspectives. Observable consider clinical-biological nature AD. Statistically significant effects or do not always equate meaningfulness. Assessment tools reflect stage-specific subtle changes following treatment. Real-world evidence will support consensus, definition, interpretation

Language: Английский

Citations

3
Timing of changes in Alzheimer's disease plasma biomarkers as assessed by amyloid and tau PET clocks DOI Open Access
Marta Milà‐Alomà, Duygu Tosun, Suzanne E. Schindler

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 28, 2024

Abstract Plasma biomarkers for Alzheimer’s disease (AD) are increasingly being used to assist in making an etiological diagnosis cognitively impaired (CI) individuals or identify unimpaired (CU) with AD pathology who may be eligible prevention trials. However, a better understanding of the timing plasma biomarker changes is needed optimize their use clinical and research settings. The aim this study was evaluate change key (Aβ42/Aβ40, p-tau217, p-tau181, GFAP NfL) from six different companies, along established biomarkers, using progression timelines based on amyloid tau PET. We data Disease Neuroimaging Initiative (ADNI), including 784 longitudinal 18 F-florbetapir PET 359 F-flortaucipir PET, estimate age at positivity, defined as first positive scan. Of these, measures were available 190 estimated positivity 70 positivity. Age stronger predictor symptom onset than 17 progressed CU CI during participation ADNI (Adj R 2 = 0.86 vs. Adj 0.38), therefore all Generalized additive mixed models (GAMMs) model trajectories across years since onset, earliest timepoint abnormality when compared reference group amyloid- tau-negative individuals, well time periods significant biomarkers. All except NfL became abnormal prior Aβ42/Aβ40 reach consistently early timeline. levels reached plateau, while increased throughout progression. Some differences observed assays. primary utility lie identification high risk AD. In contrast, increase timelines, supporting potential staging monitoring

Language: Английский

Citations

0
Age-specific control and Alzheimers disease reference curves and z-scores for glial fibrillary acidic protein in blood DOI Creative Commons
Steffen Halbgebauer, Badrieh Fazeli, Veronika Klose

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

Abstract Background Serum glial fibrillary acidic protein (GFAP) is a biomarker for astrocytic injury and astrogliosis. Concentrations are elevated in numerous neurological disorders, including pronounced increase Alzheimer’s disease (AD). However, GFAP levels the serum also with age. Consequently, integration of into clinical routine their interpretation demands age-adjusted reference values. Methods from 1273 subjects (952 non-inflammatory non-neurodegenerative controls 321 AD) were analyzed using microfluidic Ella system. Age-dependent values calculated by additive quantile regression analysis. Percentiles z-scores employed presentation as function Results All patients within AD continuum exhibited statistically comparison to control cohort (p<0.0001). This remained case when newly generated age-corrected applied In cohort, non-linear elevation increasing age was observed (Spearman correlation coefficient (r) 0.62, 95%CI 0.58-0.66, p<0.0001). contrast, more linear (0.16, 0.05-0.26, p=0.004). cut-offs different groups. The areas under curve (AUC 0.97) demonstrated excellent diagnostic test performance early onset group. effect less marked elderly 0.72). Conclusions Our novel enable practice, moving group individual level. They support both intra- interindividual single diseases pathology, an accurate discrimination disease.

Language: Английский

Citations

0