Neurogranulin (Ng) is a postsynaptic protein correlating with cognitive reserve. Low Ng indicates depleted neuronal capacity to produce p-tau217, making CSF p-tau217 unreliable. Patients with preserved Ng levels show faithful p-tau217 response to amyloid modulation. This hypothesis addresses a potentially critical prerequisite for valid p-tau217 endpoints but remains the lowest-confidence proposal requiring prospective validation.
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