Can low thiamine (vitamin B1) deficiency cause a false‑positive elevation of amyloid‑related phosphorylated tau 217 (pTau217) measured in a blood biomarker for Alzheimer’s disease?

No Evidence That Thiamine Deficiency Causes False-Positive pTau217 Elevation

There is no documented evidence that low thiamine levels produce false-positive elevations of pTau217 in Alzheimer's disease blood biomarker testing. The available literature does not identify thiamine deficiency as a known confounder or source of analytical interference for pTau217 assays.

Understanding the Relationship Between Thiamine and AD Pathology

While thiamine deficiency and AD share some overlapping features, they represent distinct pathophysiological processes:

Thiamine Deficiency Effects

• Thiamine deficiency causes cognitive decline, synaptic hypometabolism, mitochondrial dysfunction, oxidative stress, and can lead to amyloid and tau deposition through its own pathological mechanisms 1, 2, 3
• In preclinical models, reduced thiamine can drive AD-like abnormalities including memory deficits, neuritic plaques, and tau hyperphosphorylation 3
• Thiamine transport is disrupted in AD brains, with reduced expression of thiamine transporters (THTR-1 and THTR-2) in the prefrontal cortex and hippocampus of AD patients 4

Critical Distinction

This does not mean thiamine deficiency causes false-positive pTau217 results. Rather, thiamine deficiency may contribute to actual AD pathology development. If thiamine deficiency leads to genuine tau phosphorylation and amyloid deposition, an elevated pTau217 would reflect true pathological changes, not a false positive.

What pTau217 Actually Measures

Current guidelines and research establish that plasma pTau217:

• Reflects actual amyloid plaque pathology with high specificity (AUC 0.92-0.98 for detecting amyloid PET positivity) 5
• Shows strong correlation with both amyloid burden and tau pathology in AD 6, 7
• Is specific to AD and not elevated in other tauopathies (progressive supranuclear palsy, corticobasal degeneration, Pick's disease) 6
• Demonstrates 203% elevation in amyloid-positive individuals compared to amyloid-negative controls 8

Known Confounders and Interferences

The comprehensive guidelines on blood biomarker standardization and appropriate use 5, 6, 9, 7 identify several factors affecting biomarker accuracy:

Pre-analytical variables that matter:

• Blood specimen type (plasma vs. serum)
• Anticoagulant choice (EDTA preferred)
• Sample collection and processing protocols
• Storage conditions

Biological factors mentioned:

• Age and sex (requiring adjustment in analyses)
• Cerebrovascular and cardiovascular comorbidities
• Concomitant medications
• Non-AD brain injuries (particularly for GFAP)

Thiamine deficiency is notably absent from these lists of known confounders 5, 6, 9, 7.

Clinical Interpretation

If a patient presents with both cognitive impairment and suspected thiamine deficiency:

1. Elevated pTau217 likely reflects genuine AD pathology, not a false positive
2. Thiamine deficiency may be a contributing factor to cognitive decline but does not invalidate the biomarker result
3. Both conditions may coexist and require treatment
4. The comprehensive diagnostic evaluation should still include assessment for reversible causes of cognitive impairment (including nutritional deficiencies) as recommended 5, 10, 11

Important Caveat

The absence of evidence is not evidence of absence. However, given the extensive validation work on pTau217 assays across multiple platforms 8, 12, 13, 14 and the detailed guidelines on potential confounders 5, 6, 9, 7, if thiamine deficiency were a significant source of false positives, it would likely have been identified and reported in the literature.

In clinical practice, do not dismiss an elevated pTau217 result based on thiamine deficiency alone. Proceed with standard diagnostic algorithms for AD evaluation while addressing any identified nutritional deficiencies as part of comprehensive care.