In this episode, we spotlight Plenary Lecture 03, the Don Price Memorial Lecture, "Five Critical Inflection Points in Alzheimer's: Guideposts for Smarter Drug Development," from the AD/PD™ 2026 International Conference, held on March 18, 2026.
The session was chaired by Prof. Sangram Sisodia (USA) and presented by Prof. Bart De Strooper (Belgium), delivered as the third annual lecture honoring Donald L. Price, a foundational figure in Alzheimer's and neurodegeneration research.
Key highlights from this session include:
• A reframing of Alzheimer's as a staged biological process defined by critical inflection points, rather than through the late, nonspecific endpoint of dementia, by which time irreversible neuronal loss has already occurred
• A modern, qualitative amyloid hypothesis: what matters is not only how much amyloid is produced, but the shift toward longer, more aggregation-prone Aβ species such as Aβ42 and Aβ43, supported by familial APP and presenilin genetics • Evidence that microglia are active participants in amyloid fibril formation and compaction, not merely passive plaque-clearing cells
• A cellular response phase in which plaques create local "tissue domains" of glial reprogramming, with higher polygenic risk linked to stronger inflammatory responses
• Tau induction as the pivotal bridge to widespread neurodegeneration, shown using human iPSC-derived neurons transplanted into amyloid-bearing models that develop phospho-tau pathology and release plasma-detectable tau
• Evidence that pathological tau can trigger necroptosis-associated neuronal death, supported by human brain tissue and tau-seeding experiments
• The value of plasma phospho-tau217 as a breakthrough biomarker signaling the transition from an amyloid-dominant to a tau-engaged disease stage
• Therapeutic implications centered on timing — why anti-amyloid antibodies work by engaging microglia yet offer only modest late-stage benefit, and why gamma-secretase modulators and mechanism-based anti-tau strategies may prove more precise
Prof. De Strooper closed with a threshold-based framework in which each brain is a mosaic of tissue domains at different disease stages — implying that combination therapy will likely be necessary and that biomarker-guided intervention must come as early as possible. The central message for clinicians and researchers was clear: the key challenge is no longer only what to target, but when to intervene, matching the right mechanism to the right disease phase.
This episode is particularly relevant for neurologists, neuroscientists, translational scientists, clinical trialists, biotech and pharma professionals, biomarker researchers, and academic investigators working across Alzheimer's disease and neurodegeneration.
This podcast was created using AI to provide a concise and insightful summary of an AD/PD™ 2026 session. While every effort has been made to ensure accuracy, listeners are encouraged to consult official conference materials for detailed information.
The AD/PD™ 2026 International Conference on Alzheimer's and Parkinson's Diseases and related neurological disorders took place March 17–21, 2026, in Copenhagen, Denmark.
🔗 https://adpd.kenes.com
