The Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART) is a global network of scientists, clinicians and dementia professionals. ISTAART represents a community dedicated to advancing Alzheimer’s and dementia research by fostering education, collaboration, and innovation across disciplines.  

In addition to hosting the annual Alzheimer’s Association International Conference (AAIC), ISTAART provides its members year-round opportunities to engage in scientific exchange, including the Alzheimer’s and Dementia Research Webinar series that share the latest advances in the research and care for Alzheimer’s and dementia. 

We recently tuned in to the Biofluid Based Biomarkers (BBB) Professional Interest Area (PIA) 2024 Year In Review webinar presented by Dr. Laia Montoliu-Gaya, Assistant Professor from the University of Gothenburg, and an internationally recognized pioneer in the field of fluid biomarkers for AD diagnosis and prognosis. Dr. Montoliu-Gaya walked the audience through relevant research published in the year 2024, focusing on three key themes: 

• The rapidly advancing research and evolving landscape of blood Tau biomarkers 
• Considerations for the clinical implementation of blood biomarker tests 
• Other relevant findings and trends in neurodegeneration disease research 

Blood Tau Biomarkers   

Dr. Montoliu-Gaya started by discussing updated criteria for diagnosing and staging AD.¹ The new criteria re-established the fundamental principles that add more weight on characterizing AD by its biology, emphasizing the role of biomarkers in AD diagnosis. In the updated criteria, biomarkers are grouped into three broad categories: core biomarkers of AD neuropathology, non-specific biomarkers that are important in AD pathogenesis but are also involved in other brain diseases, and biomarkers of common non-AD co-pathologies. Multiple fluid biomarkers, including plasma biomarkers, such as the p-Tau variants (p-Tau 181, p-Tau 217 and p-Tau 231) and emerging Tau biomarkers like MTBR-Tau and mid-region Tau fragments, are enlisted as core biomarkers. NfL and GFAP continue to be recommended as non-specific markers and α -synuclein is recognized for its value as a co-pathology biomarker.  

With burgeoning biomarkers, understanding how they compare in diagnostic performance is key. Several publications reported results from studies comparing the diagnostic accuracy of various markers across different methods. Of note, plasma p-Tau 217 consistently shows high diagnostic accuracy, regardless of the detection methods, which is equivalent or superior to some of the established CSF biomarkers, even at early stages of the disease.^2,3  

In addition to diagnosis, immunoassay-based fluid biomarkers are increasingly valued for the staging of AD, which helps improve the diagnosis and prognosis and subject stratification in clinical trials.⁴ Additionally, emerging Tau markers including p-Tau 212, p-Tau 205 and brain-derived Tau (BD-Tau) and N-terminal Tau (NTA-Tau) are showing promise in improving AD staging for Tau pathology and neurodegeneration.^{5,6, 7,8} 

Notably, the Single Molecular Array (Simoa®) technology is one of the most widely used technologies for fluid biomarker measurement in the studies published in 2024.  

Considerations for the clinical implementation of blood biomarker tests 

With anti-amyloid treatments available, the need for biomarker confirmation of amyloid pathology for early symptomatic AD is increasing, with blood-based biomarker (BBM) tests being viewed as more accessible and scalable than CSF tests and PET scans. Given the large variety of tests available, the Global CEO Initiative provided recommendations on minimum acceptable diagnostic performance of BBM tests for clinical use, one and two cut-off approaches, and best practices in interpreting test results in the complete clinical context.¹⁰ Multiple publications also explore BBM implementation in clinical settings, including primary care, secondary care and treatment & follow-up.^{9, 10} 

Dr. Montoliu-Gaya also touched upon publications that investigated population-level use of AD BBM, variations in baseline levels and longitudinal changes, and variations associated with sex and racial differences, among others.  

Co-pathology is a known challenge in AD research and care. Dr. Montoliu-Gaya highlighted Lewy body pathology as a common co-pathology in AD, and the increasing relevance of α-Synuclein as a biomarker in the context of AD.  

Other relevant findings  

Broadening the focus to non-AD neurodegenerative diseases, Dr. Montoliu-Gaya shared recent advancement in biomarker research in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). One study reported the potential of using TDP-43 and a ratio of 3R/4R Tau measured from extracellular vesicles (EV) to improve differential diagnosis FTD and ALS.¹¹ A multi-marker blood test interpretation tool that includes plasma p-Tau, GFAP, and NfL has enabled high accuracy in differentiating Alzheimer’s from dementia with Lewy bodies.¹² Another study investigating 17 synaptic proteins as potential biomarkers for synaptic dysfunction and degeneration in a spectrum of neurodegenerative diseases reported that SNAP-25 and 14-3-3 zeta/delta are promising  synaptic biomarkers for AD, while neuronal pentraxins may be suitable as a general indicator of cognitive decline.¹³ 

In vivo CSF proteomic studies are emerging and uncovering novel molecular events and protein signatures associated with different stages of AD pathology, offering new insights into AD disease course, potential biomarkers, and treatment strategies.¹⁴ 

Lastly, Dr. Montoliu-Gaya introduced the innovative dried blood spot (DBS) or dried plasma spot (DPS) sampling for biomarker testing. DBS/DPS uses a simple device to collect drops of blood from a finger prick, which can be stored at ambient temperature. A wide array of AD biomarkers is detectable from DBS/DPS samples, using the Simoa® technology, and correlate with measurement from standard procedures. DBS/DPS represents a potentially more accessible and cost-efficient sampling method than standard blood collection, enabling broader, earlier, and remote use of AD biomarker testing.¹⁵ 

Future Challenges and Closing Remarks  

In conclusion, Dr. Montoliu-Gaya and the panelists alluded to some of the future challenges, highlighting the need for more fluid biomarker research in the following areas: 

• Biomarkers for neurodegenerative diseases other than AD 
• Biomarkers for staging, prognosis, and treatment monitoring, especially in specialized AD medicine  
• Biomarkers from dried blood/plasma spot tests 

Overall, 2024 witnessed great advancements in both research and publications in the AD fluid biomarker field with an exciting outlook for 2025. 

ISTAART members can access a recording of this webinar here. 

To learn how Quanterix’s neurology biomarker assay solutions can empower your research in neurodegenerative diseases download the Blood Biomarkers of Brain Health brochure.

References

• 1. Jack CR Jr, Andrews JS, Beach TG, et al. Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimers Dement. 2024;20(8):5143-5169. doi:10.1002/alz.13859 
• 2. Therriault J, Woo MS, Salvadó G, et al. Comparison of immunoassay- with mass spectrometry-derived p-tau quantification for the detection of Alzheimer’s disease pathology. Mol Neurodegener. 2024;19(1):2. Published 2024 Jan 7. doi:10.1186/s13024-023-00689-2 
• 3. Barthélemy NR, Salvadó G, Schindler SE, et al. Highly accurate blood test for Alzheimer’s disease is similar or superior to clinical cerebrospinal fluid tests. Nat Med. 2024;30(4):1085-1095. doi:10.1038/s41591-024-02869-z 
• 4. Salvadó G, Horie K, Barthélemy NR, et al. Disease staging of Alzheimer’s disease using a CSF-based biomarker model. Nat Aging. 2024;4(5):694-708. doi:10.1038/s43587-024-00599-y 
• 5. Kac PR, González-Ortiz F, Emeršič A, et al. Plasma p-tau212: antemortem diagnostic performance and prediction of autopsy verification of Alzheimer’s disease neuropathology. Preprint. medRxiv. 2023;2023.12.11.23299806. Published 2023 Dec 11. doi:10.1101/2023.12.11.23299806 
• 6. Lantero-Rodriguez J, Montoliu-Gaya L, Benedet AL, et al. CSF p-tau205: a biomarker of tau pathology in Alzheimer’s disease. Acta Neuropathol. 2024;147(1):12. Published 2024 Jan 6. doi:10.1007/s00401-023-02659-w 
• 7. Lantero-Rodriguez J, Salvadó G, Snellman A, et al. Plasma N-terminal containing tau fragments (NTA-tau): a biomarker of tau deposition in Alzheimer’s Disease. Mol Neurodegener. 2024;19(1):19. Published 2024 Feb 17. doi:10.1186/s13024-024-00707-x 
• 8. Gonzalez-Ortiz F, Kirsebom BE, Contador J, et al. Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer’s disease. Nat Commun. 2024;15(1):2908. Published 2024 Apr 4. doi:10.1038/s41467-024-47286-5 
• 9. Schindler SE, Galasko D, Pereira AC, et al. Acceptable performance of blood biomarker tests of amyloid pathology – recommendations from the Global CEO Initiative on Alzheimer’s Disease. Nat Rev Neurol. 2024;20(7):426-439. doi:10.1038/s41582-024-00977-5 
• 10. VandeVrede L, Schindler SE. Clinical use of biomarkers in the era of Alzheimer’s disease treatments. Alzheimers Dement. 2025;21(1):e14201. doi:10.1002/alz.14201 
• 11. Chatterjee M, Özdemir S, Fritz C, et al. Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS. Nat Med. 2024;30(6):1771-1783. doi:10.1038/s41591-024-02937-4 
• 12. Verberk IMW, Jutte J, Kingma MY, et al. Development of thresholds and a visualization tool for use of a blood test in routine clinical dementia practice. Alzheimers Dement. 2024;20(9):6115-6132. doi:10.1002/alz.14088 
• 13. Nilsson J, Pichet Binette A, Palmqvist S, et al. Cerebrospinal fluid biomarker panel for synaptic dysfunction in a broad spectrum of neurodegenerative diseases. Brain. 2024;147(7):2414-2427. doi:10.1093/brain/awae032 
• 14. Pichet Binette A, Gaiteri C, Wennström M, et al. Proteomic changes in Alzheimer’s disease associated with progressive Aβ plaque and tau tangle pathologies. Nat Neurosci. 2024;27(10):1880-1891. doi:10.1038/s41593-024-01737-w 
• 15. Huber H, Blennow K, Zetterberg H, et al. Biomarkers of Alzheimer’s disease and neurodegeneration in dried blood spots-A new collection method for remote settings. Alzheimers Dement. 2024;20(4):2340-2352. doi:10.1002/alz.13697