Autor:innen:
Gwendlyn Kollmorgen, Penzberg (Germany)
Kaj Blennow, Mölndal (Sweden)
Jeffrey Dage, Indianapolis (United States)
Sterling Johnson, Madison (United States)
Eric M. Reiman, Phoenix (United States)
Leslie Shaw, Philadelphia (United States)
Maryline Simon, Rotkreuz (Switzerland)
Udo Eichenlaub, Penzberg (Germany)
Tobias Bittner, Basel (Switzerland)
Vivienne Stutz, Rotkreuz (Switzerland)
Simone Wahl, Penzberg (Germany)
Norbert Wild, Penzberg (Germany)
Richard Batrla, Rotkreuz (Switzerland)
José Luis Molinuevo, Barcelona (Spain)
Introduction
Biomarker assays may support differential diagnosis, monitor progression and assess treatment response in patients with neurodegenerative diseases, including Alzheimer’s disease. Current assays for cerebrospinal fluid (CSF) biomarkers provide limited robustness and lot-to-lot comparability. Thus, more robust assays are needed to enable cross-trial comparison of high-quality biomarker data. A unified statistical analysis package covering five aspects may help to achieve that aim: descriptive biomarker analysis, association with clinical outcome, relationship with disease progression, correlation between biomarkers in multivariate analyses, and longitudinal changes over time in the context of age and disease-pathology severity.
Methods
Biomarker assays that may be used in exploratory CSF settings include amyloid-β (1–42), amyloid-β (1–40), α-synuclein, GFAP, IL-6, neurogranin, NFL, pTau, S100B, sTREM2, tTau, and YKL-40. The analysis may generate evidence for biomarker utility from highly characterized cohorts (incl Wisconsin Registry for Alzheimer’s Prevention) and may precisely monitor longitudinal disease changes. Correlation between biomarkers and progression from normal cognition to mild cognitive impairment will offer insights into disease pathology. Identification of patients with co-pathologies may assist in understanding treatment responses and selecting candidates for alternative dosing/treatments. Future biomarkers may cover inflammation, vascular dysfunction, synaptic dysfunction (eg SNAP-25), autophagy, mitochondrial dysfunction, amyloid-β oligomers, additional tau epitopes, and TDP-43. This “NeuroToolKit” approach could be realized using the Roche Elecsys® platform with robust prototype assays.
Conclusions
Such a “NeuroToolKit” approach could generate comparable clinical biomarker data across several cohorts, thus supporting decision-making regarding clinical utility of biomarkers in neurodegenerative diseases across academia and industry.