Synaptic Overdrive Drives Childhood Dementia

Patient‑derived cortical circuits from children with Sanfilippo syndrome show escalating excitatory synaptic activity as neurons mature, making synaptic dysfunction an early driver rather than a late byproduct. The hyperexcitability also increases vulnerability to metabolic stress, suggesting environmental or physiological insults can speed progression. — If early synaptic overactivity initiates degeneration, research, diagnostics, and regulatory pathways should shift toward earlier intervention, synapse‑targeted drugs, and gene/stem‑cell trials designed for developmental windows.