Assessing metrics in neurodegenerative disease research

Millions of people are affected by neurodegenerative diseases (NDs) worldwide, with increased risks associated with contributing factors such as age, genetics, and environmental conditions. All NDs are characterized by the loss of neurons, resulting in cognitive or functional impairment, or sometimes both.

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For instance, Alzheimer’s disease (AD), Creutzfeldt-Jakob disease, and frontotemporal dementia (FTD) are clinical conditions that primarily cause cognitive decline, while Parkinson’s disease (PD), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) – the condition that Stephen Hawking suffered from – affect motor function.

One of the main challenges when it comes to delivering a diagnosis of any of these conditions is the high correlation between symptoms, especially those that cause cognitive impairment.

However, recently conducted research has been able to identify several key proteins that can support ND characterization. This has led to the development of assays – such as those that Tecan offers – that could help to further support clinicians and researchers in the field. 

Protein power

In recent decades, several NDs have been categorized as neurodegenerative proteinopathies as they result in the pile-up of misfolded proteins in the brain. These abnormal protein conformations, also known as amyloid, are believed to be the cause of around 50 conditions and are likely influenced by primary amyloid-forming proteins that make different contributions toward disease prognosis.1

Therefore, resolving such protein patterns at the proteoform level, a distinct molecular variant of a protein that involves post-translational modifications could transform approaches in how these disorders are diagnosed and treated.

In the meantime, assays are available to measure several of the proteins believed to be involved in cerebrospinal fluid (CSF) and serum, potentially supporting the diagnosis and management of several conditions. 

Alzheimer’s disease (AD)

Since the early nineties, AD has been one of the most common neurodegenerative proteinopathies and, as a result, has garnered significant attention as a subject of research.

Current theory suggests that individuals with AD typically display decreased levels of amyloid-beta 1-42 (Aβ1-42) and increased levels of tubulin-associated unit (TAU) compared to their healthy counterparts.

Nevertheless, as these proteins are also implicated in the pathogenesis of other neurodegenerative diseases, it is imperative to measure additional proteins concurrently to enhance diagnostic precision.

For instance, increased TAU levels in the brain are also typical of FTD, but raised phosphorylated TAU (pTAU) is characteristic of AD alone, so measuring both markers can aid in accurate differential diagnosis.

Moreover, measuring Aβ1-42 in isolation can generate false positive or negative results, but the ratio of Aβ1-42 to amyloid-beta 1-40 (Aβ1-40) has demonstrated its capacity to be a much better diagnostic marker for AD.2

This can help to discern between AD and other dementias, such as vascular dementia, dementia with Lewy bodies, and FTD.3

These proteins are covered in extensive detail in the latest paper by the International Working Group for AD, which acknowledges the fact that AD diagnosis should be based on both clinical and biological characteristics, advising Aβ1-42, Aβ1-40:Aβ1-42 ratio and pTAU as preferred biomarkers.4


Another series of biomarkers receiving attention for the management of NDs is neurofilament proteins. These are structural components of myelinated axons on neurons, which determine the shape and diameter of the axon and take up a central role in signal propagation.

When it comes to managing various NDs, the neurofilament light chain (NF-L) is a subunit that is of particular interest as its level increases in the CSF and blood in relation to the degree of axonal damage.5 The ability to identify and quantify axonal damage could boost diagnostic and prognostic accuracy for a number of diseases, including MS and ALS.5

Multiple sclerosis

The debilitating symptoms patients with MS suffer are caused by demyelination of neurons, leading to axonal degradation. Resultingly, neurofilaments are released into the CSF, giving rise to the concentration levels of NF-L.6

Therefore, increased NF-L levels in CSF could be used as a marker in MS for prognosis in clinically isolated syndrome (the initial onset of MS), as well as relapsing-remitting MS.

Additionally, monitoring NF-L levels could be key for evaluating treatment success.7 NF-L can also be detected in the serum of patients with MS, with numerous studies bringing attention to the link between serum and CSF NF-L levels, suggesting that blood sampling has the potential to eventually replace CSF testing.6,8

Amyotrophic lateral sclerosis

Elevated NF-L is found in both CSF and serum of patients with ALS, and a rising amount of evidence gives credibility to using NF-L as an accurate biomarker for this condition.9

This biomarker also has the potential to improve diagnostic accuracy at first presentation, as NF-L levels were found to be considerably higher in patients with the onset of early symptoms.10

It is also believed to boost prognostic accuracy, as it has the capacity to closely measure patients’ pharmacodynamic response to treatment.9

With the number of people being diagnosed and living with neurodegenerative diseases increasing, finding new, innovative methods to advance diagnosis and monitor treatment is key.

The novel biomarkers outlined in this article offer greater insights to help distinguish between conditions for patients presenting with similar symptoms, potentially supporting earlier diagnosis and treatment monitoring. 

To discover more or to browse Tecan’s full portfolio, visit


  1. Noor A, et al. Neurodegenerative Proteinopathies in the Proteoform Spectrum-Tools and Challenges. Int J Mol Sci. 2021;22(3):1085. doi: 10.3390/ijms22031085.
  2. Wiltfang J, et al. Amyloid beta peptide ratio 42/40 but not A beta 42 correlates with phospho-Tau in patients with low- and high-CSF A beta 40 load. J Neurochem. 2007;101(4):1053-9. doi: 10.1111/j.1471-4159.2006.04404.x.
  3. Spies PE, et al. The cerebrospinal fluid amyloid beta42/40 ratio in the differentiation of Alzheimer’s disease from non-Alzheimer’s dementia. Curr Alzheimer Res. 2010;7(5):470-476. doi:10.2174/156720510791383796.
  4. Dubois B, et al. Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group. Lancet Neurol. 2021;20(6):484-496. doi:10.1016/S1474-4422(21)00066-1.
  5. Gaetani L, et al. Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry. 2019;90(8):870-881. doi:10.1136/jnnp-2018-320106.
  6. Novakova L, et al. Monitoring disease activity in multiple sclerosis using serum neurofilament light protein. Neurology. 2017;89(22):2230-2237. doi:10.1212/WNL.0000000000004683.
  7. Varhaug KN, et al. Neurofilament Light Chain as a Biomarker in Multiple Sclerosis. Front Neurol. 2019;10:338. doi:10.3389/fneur.2019.00338.
  8. Kuhle J, et al. Blood neurofilament light chain as a biomarker of MS disease activity and treatment response. Neurology. 2019;92(10):e1007-e1015. doi:10.1212/WNL.0000000000007032.
  9. Lu CH, et al. Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis [published correction appears in Neurology. 2015;8;85(10):921]. Neurology. 2015;84(22):2247-2257. doi:10.1212/WNL.0000000000001642
  10. Feneberg E, et al. Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis. Neurology. 2018;90(1):e22-e30. doi:10.1212/WNL.0000000000004761.

About Tecan

​Tecan is a leading global provider of automated laboratory instruments and solutions. Its systems and components help people working in clinical diagnostics, basic and translational research and drug discovery bring their science to life.

In particular, the company develops, produces, markets and supports automated workflow solutions that empower laboratories to achieve more. Its Cavro branded instrument components are chosen by leading instrumentation suppliers across multiple disciplines.

Tecan works side by side with a range of clients, including diagnostic laboratories, pharmaceutical and biotechnology companies and university research centers. Its expertise extends to developing and manufacturing OEM instruments and components, marketed by its partner companies. Whatever the project – large or small, simple or complex – helping its clients to achieve their goals comes first.

The company holds a leading position in all the sectors it works in, and has changed the way things are done in research and development labs around the world. In diagnostics, for instance, it has raised the bar when it comes to the reproducibility and throughput of testing.

In under four decades, Tecan has grown from a Swiss family business to a brand that is well established on the global stage of life sciences. From pioneering days on a farm to the leading role the business assumes today, Tecan empowers research, diagnostics and many applied markets around the world.

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Last updated: Jun 10, 2024 at 9:57 AM


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