Conditions Other Than Alzheimer's Disease That Can Cause Elevated P-tau 217
Elevated plasma p-tau217 is highly specific to Alzheimer's disease pathology and is NOT significantly elevated in other tauopathies or neurodegenerative diseases. 1
Primary Finding: P-tau 217 Specificity to Alzheimer's Disease
The most critical evidence shows that increased plasma p-tau217 levels have specifically been observed in AD and not in other tauopathies, including: 1
- Primary age-related tauopathy - no significant elevation 1
- Progressive supranuclear palsy (PSP) - no significant elevation 1, 2
- Corticobasal degeneration/syndrome - no significant elevation 1, 2
- Pick's disease - no significant elevation 1
- Frontotemporal lobar degeneration (FTLD) syndromes - no significant elevation 2, 3
- Subcortical ischemic vascular dementia (SIVD) - no significant elevation 3
Diagnostic Performance Against Non-AD Conditions
Plasma p-tau217 demonstrates exceptional ability to differentiate AD from other neurodegenerative diseases, with levels increased 250-600% in AD dementia compared to non-AD neurodegenerative diseases, with p-tau217 showing the largest relative increases. 1
Specific discrimination performance:
- AD syndromes vs. FTLD syndromes: AUC = 0.93, significantly outperforming p-tau181 2
- Pathology-confirmed AD vs. pathology-confirmed FTLD: AUC = 0.96 2
- AD dementia vs. SIVD: AUC = 0.892 3
- AD dementia vs. cognitively unimpaired controls: AUC = 0.98 2
Potential Confounding Factors (Not True Elevations)
While p-tau217 is not elevated in other neurodegenerative diseases, certain factors may influence p-tau217 measurements and require careful interpretation: 4
- Cerebrovascular disease - may affect interpretation 4
- Cardiovascular disease - may affect interpretation 4
- Age - biological confounder 5
- Creatinine levels - biological confounder 5
- Depressive symptoms - biological confounder 5
Critical Clinical Pitfall
The key clinical implication is that elevated p-tau217 is essentially pathognomonic for Alzheimer's disease pathology when using high-performing assays. 1, 2 If p-tau217 is elevated in a patient with dementia, this strongly indicates AD pathology rather than other neurodegenerative conditions. 1, 2, 3
When p-tau217 is normal but cognitive impairment exists, clinicians should actively consider alternative diagnoses such as frontotemporal dementia or corticobasal degeneration. 5
Assay Quality Considerations
Not all p-tau assays perform equally, and clinicians must use validated high-performing platforms including Quanterix Simoa, Lumipulse G, IP-MS methods, or emerging NULISA technology to ensure accurate results. 4, 5 Lower-performing assays may produce misleading results. 1