COLBOS mutation may delay Alzheimer's by decades via enhanced reelin signaling
A COLBOS gene variant linked with PSEN1-related early-onset Alzheimer’s appears to boost reelin signaling by strengthening its binding to heparan sulfate, keeping reelin at neuron surfaces where it helps slow tau phosphorylation and amyloid buildup. This protective effect can delay disease onset by about 20 years in some patients, though it does not prevent the disease. The finding suggests that therapies aiming to enhance reelin signaling could delay Alzheimer's in a broad patient population, with gene-therapy approaches being explored.