From the Guidelines
P-tau in the indeterminate range means that the phosphorylated tau protein levels in cerebrospinal fluid (CSF) fall between normal and abnormal values, creating diagnostic uncertainty. This result alone cannot definitively confirm or rule out Alzheimer's disease or other neurodegenerative conditions. When p-tau results are indeterminate, clinicians typically consider them alongside other biomarkers like amyloid-beta levels, total tau, clinical symptoms, cognitive testing, and neuroimaging findings to form a complete diagnostic picture. Some key points to consider in the interpretation of p-tau levels include:
- Indeterminate results may indicate early disease stages, mild pathology, or other conditions affecting tau metabolism.
- Follow-up testing after 6-12 months may be recommended to track changes over time.
- P-tau is significant because abnormal phosphorylation of tau protein leads to the formation of neurofibrillary tangles, a hallmark of Alzheimer's disease pathology, making it a valuable but not standalone biomarker in the diagnostic process. As noted in the study by 1, the use of CSF biomarkers, including p-tau, can aid in the diagnosis of Alzheimer's disease, particularly in cases where the diagnosis is uncertain. The study by 2 also highlights the importance of considering multiple biomarkers and clinical factors when interpreting p-tau results, as the levels of CSF Ab1–42, tau, and p-tau can be conflicting, and other biomarkers or imaging modalities may be needed to clarify the diagnosis. Overall, the interpretation of p-tau levels in the indeterminate range requires a comprehensive approach, taking into account multiple factors and biomarkers, as recommended by the studies 1, 2, 3, 4.
From the Research
p-tau in Indeterminate Range Meaning
- p-tau levels can be used as a biomarker to differentiate between patients with Alzheimer's disease (AD) and those with other neurodegenerative diseases, such as idiopathic normal-pressure hydrocephalus (iNPH) 5.
- An indeterminate range of p-tau levels may indicate a need for further testing or evaluation to determine the underlying cause of cognitive impairment or other symptoms 6, 7.
- Studies have shown that low levels of p-tau are associated with a good clinical outcome in patients with iNPH, while high levels are associated with AD 7, 5.
- The use of p-tau as a biomarker can help identify patients with AD pathology, particularly in those with traumatic encephalopathy syndrome (TES) 6.
- However, p-tau levels may not be useful in differentiating between patients with TES who do not have AD pathology 6.
Diagnostic Considerations
- p-tau levels should be considered in conjunction with other diagnostic markers, such as amyloid-beta (Aβ) and total tau (t-tau) protein, to improve diagnostic accuracy 5.
- The interpretation of p-tau levels may be influenced by factors such as age, sex, and ethnicity 5.
- Further research is needed to fully understand the role of p-tau in the diagnosis and management of neurodegenerative diseases 6, 8.