Potential use for blood biomarkers in dementia diagnosis where medical resources are limited

In a systematic review of 13 studies involving 3 blood biomarkers (published in the Journal of Alzheimer's Disease, Feb 2026), our paper indicates how diagnostic blood tests can be impactful in real-world settings, notably in countries which have fewer health facilities. The research notes that they are more scalable than PET and CSF, and could significantly increase access to biomarker-supported diagnoses. Increased accessibility can ‘democratise’ diagnosis as it is more easily deployed in Lower- and Middle-income countries where currently 60% of people with dementia live.  

Gold standard diagnostic techniques

Up to now, the gold standard for dementia diagnosis has been either a PET scan or cerebrospinal fluid (CSF) lumbar puncture. These procedures are much more likely to be available in higher income countries.

The development of highly sensitive blood-based tests to detect and diagnose Alzheimer’s presents a highly resource-efficient, non-invasive and accessible alternative to these more expensive and non-scalable techniques.

It is anticipated that blood biomarkers will achieve regulatory approval in the near future and commercial plasma biomarker tests are going to play an increasing role in clinical services, given the advent of disease modifying therapies evidenced by drugs like lecanemab and aducanumab.

Biomarkers selected for comparison

In a paper published in February 2026, Shivani Suresh describes looking at 3 blood biomarkers which have been highlighted as clinically relevant by the National Institute on Aging and the Alzheimer’s Association, synthesising 13 studies between January 2019 and January 2025.

1. pTau217 is a biomarker associated with AD
2. glial fibrillary acidic protein (GFAP)
3. neurofilament light chain (NfL) – NfL is a non-specific biomarker of neurodegeneration, especially in disorders of cognitive dysfunction.

The study only looked at data from memory clinics, neurology departments, or clinical cohorts – as they represent real-world healthcare services and clinically representative patient groups.

Study Outcomes

Of the 3 studied, pTau217 shows consistently high accuracy (AUC > 0.90) across all studies for Alzheimer’s disease and promise for diagnosis of AD.

GFAP and NfL both displayed inconsistent results, but may provide complementary information, particularly for differential diagnosis of both cognitive impairment and other dementias.

NfL is a non-specific biomarker of neurodegeneration, especially in disorders of cognitive dysfunction.  Two independent evaluations of NfL reported moderate diagnostic accuracy and each demonstrated that the diagnostic performance of plasma NfL was equivalent to its CSF counterpart, suggesting increased clinical utility and scalability.

Although GFAP sometimes showed high accuracy in specific comparisons, such as against amyotrophic lateral sclerosis and spinocerebellar ataxia, its overall diagnostic performance was variable.

Eleven out of the selected thirteen studies reported both diagnostic (Alzheimer’s versus cognitively unimpaired (CU)) and differential diagnostic (Alzheimer’s versus other neurodegenerative diseases) comparisons. Two studies reported differential diagnosis alone.

Of the three biomarkers of interest, only pTau217 consistently had an accuracy of >0.90 across all studies, and all twelve diagnostic comparisons. Although GFAP generally showed stronger diagnostic performance than NfL, especially in distinguishing Alzheimer’s from other dementias, the performance of both these biomarkers was moderate and varied. Of the thirty diagnostic comparisons in which GFAP was evaluated, six had an AUC > 0.90, sixteen had an AUC >0.75–0.90, and eight reported AUC < 0.75. Twenty-four comparisons were investigated for NfL, of which only one had an AUC > 0.90.

Need for more inclusive studies to account for population diversity

There is, in general, a need to standardise data reporting and to make studies more representative of diverse populations. Only 2 of the 13 studies reviewed included Asian populations.

There is a clear paradox in the evidence in most research:  validation studies for blood-based biomarkers are concentrated in high-income settings, yet the greatest benefit for low cost and scalable diagnostics is global, particularly where access to PET and CSF is limited. In other words, in low- and middle-income settings. So, evidence is not actually being fully tested in real-world settings.

For the future, the next steps in evaluating blood biomarkers in real-world settings needs to include criteria such as ethnicity, gender, and educational levels in both LMICs and HICs.   

Further standardized studies in underrepresented populations are required to validate and enable blood biomarker implementation in real-world clinical settings.