Abigail Mariga

Conventional animal models, from MPTP rodents to amyloid/tau transgenics, no longer provide sufficient confidence that Alzheimer’s or Parkinson’s candidates will translate to patients. As the field pivots to next-generation in vitro systems, this workshop compares advanced platforms across tau, α-synuclein, and emerging mechanisms. Attendees will explore how to link cellular potency to CSF biomarkers and translate those signals into IND-ready decision-making for both AD and PD.

Key Questions to be Addressed:

• Physiological relevance: How can we improve in vitro assays to capture endogenous tau and α-synuclein pathology without relying on artificial overexpression? What lessons can we draw from limitations of in vivo models like MPTP or transgenics?
• Assay design: What are best practices for high-throughput, image-based aggregation assays that can differentiate seeded aggregation from de novo misfolding, while retaining scalability and signal clarity?
• Biomarker linkage: How can in vitro tau and α-synuclein potency readouts be more reliably tied to in vivo CSF biomarker outcomes such as pTau181, pTau217, or α-synuclein seed assays? What magnitude of effect or PK/PD relationship should be demanded preclinically?
• Readouts for IND-enabling packages: Which cellular biomarkers (aggregation, synaptic function, neuroinflammation, resilience, mitochondrial stress) are most predictive for Alzheimer’s and Parkinson’s? How can imaging, transcriptomic, or multi-omic readouts guide clinical endpoints?
• Next-generation models: With mechanisms like gut–brain axis signaling, ferroptosis, lipid metabolism, and resilience genetics on the horizon, how should in vitro systems evolve? Are organoids, co-cultures, or iPSC-derived platforms ready for prime time in AD and PD drug discovery?