Alzheimers disease and psychiatric polygenic risk are disease-specific and independent of plasma biomarkers in a real-world young-onset dementia cohort.

In a European-ancestry young-onset dementia cohort (MiND), the AD polygenic risk score is linked to Alzheimer’s disease (OR 1.69 per SD, 95% CI 1.17–2.45) but not primary psychiatric disorder.

• Why it matters: Young-onset dementia is often misdiagnosed when neurodegenerative and primary psychiatric disorders overlap, and it is unclear whether late-onset or cross-disorder genetic risk transfers to these presentations or tracks with current plasma pathology.
• What they did: Among 687 MiND participants, AD, PSY, frontotemporal dementia, Lewy body dementia, and Parkinson’s disease PRS (PRS CS, excluding APOE) were tested across diagnostic groups, and plasma NfL, GFAP, and p-tau217 were available for 332.
• The result: No PRS was associated with any plasma protein, and combining AD PRS with plasma markers did not improve discrimination for distinguishing PPD from oNDG (AUC 0.764 for NfL alone vs 0.773 combined).

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