Shining a light on Alzheimer’s: An interview with Dr Dany Mercan, Unilabs Clinical Pathologist and Head of Medical at Unilabs Switzerland

Alzheimer's disease, the most common form of dementia, robs millions of people worldwide of their memories, cognitive abilities, and independence. To deepen our understanding of Alzheimer's, we spoke with Dr Dany Mercan, Unilabs Clinical Pathologist and Head of Medical at Unilabs Switzerland.

Diagnosing and managing Alzheimer's disease comes with unique challenges. What are some of the primary obstacles you encounter in your practice, and how is Unilabs helping to address them?

Alzheimer’s disease (AD) is biologically characterised by amyloid β (Aβ) extracellular senile plaque accumulation and 181-phosphorylated tau protein intracellular accumulation leading to neurosynaptic degeneration. The current diagnostic framework is called the ATN (Amyloid, Tau, Neurodegeneration) framework.

Currently, validated diagnostic markers for AD are measured in cerebrospinal fluid (CSF). Obtaining CSF requires specialised laboratory expertise, making it impractical for screening large populations.

Other tools include Magnetic Resonance Imaging (MRI), which can show changes in brain tissue structure; 18-fluorodesoxyglucose PET scans, which provide information on metabolic activity; and various amyloid PET scans, which can show amyloid substance deposit. The main issue with these methods is cost and availability, particularly for PET techniques, which require a cyclotron to produce the necessary radioactive tracers.

A recent study also highlighted an additional challenge: the possible heterogeneous genetic nature of what is being diagnosed as AD but is displaying clinical heterogeneity. Overall, these factors delay the time of diagnosis and therefore reduce therapeutic efficiency, as earlier intervention is expected to show greater benefits.

One of the best things we can do for Alzheimer’s patients is to remove barriers to diagnosis and support early detection of AD. One way we are doing this is through a partnership with C2N, a pioneer in advanced diagnostic solutions in the field of AD and related neurological disorders. C2N’s Precivity portfolio of blood tests aid healthcare providers and researchers in the detection of amyloid plaques and tau tangles in the brain. They also help to inform medical management and treatment decisions based on the underlying causes of dementia. 

Which of the established diagnostic techniques or biomarkers do you find particularly effective in diagnosing Alzheimer's disease currently?

Currently, the main tools for diagnosing AD are clinical diagnostic, CSF testing, and MRI and, as I mentioned above, promising new methods are also on the horizon.

The usual positive in vitro diagnostics (IVD) findings in CSF are a fall in Aβ42/Aβ40 ratio, an increase in total tau, as well as in p-tau 181. Such findings are indicative of a risk of evolution to AD if the measurements are done when the first cognitive signs appear. MRI implies that morphological changes have taken place, but these changes occur later in the disease process, and is currently better for ruling out AD rather than confirming it.

Brain biopsies may be prescribed in rapidly evolving dementia and offer the only definitive diagnosis, but they are not practical for general use.

How important is collaboration among healthcare professionals in ensuring holistic patient management?

A holistic approach can help us to reduce the burden of the disease, considering its complex set of risk factors.

The main familial risk of AD comes from apolipoprotein E Ɛ4 allele, although around 40 other genes may contribute. Twin studies suggest up to 60-80% of factors leading to AD are inheritable. Other risk factors include age, female gender, poorly controlled hypertension, smoking, and repeated head trauma.

We know that some factors can delay the onset of AD, such as a higher education level, intellectual activities, social interactions, and familial support, so identifying at-risk members of the community and encouraging some of these factors may help in reducing the onset of AD.

In cases where AD does develop, strong collaboration allows us to see how all branches of the diagnostic services interact providing lab results, imaging, genetic evaluation, counselling and, if need be, pathology.

What are some of the most promising advancements or developments on the horizon for improving Alzheimer's disease diagnosis and treatment?

Clear identification of genetic variants through more precise diagnostics can help to develop and validate future therapeutic solutions, initiating a virtuous circle of medical progress.  At Unilabs, as well as offering state-of-the-art solutions in several laboratories, we also closely monitor scientific literature, to ensure we are ready for new developments. 

We expect immense progress soon, as new blood markers are performing well and at least one (percentage of circulating phosphorylated p-Tau 217) is being developed for automated routine diagnostics. This will finally enable mass screening through easily accessible IVD. Early detection may lead to better care as treatment is more effective in the early stages of the disease. It may also help with planning ahead for support and resources.

Therapeutic options have also been expanding, with some treatments targeting symptoms like cholinesterase inhibitors and others targeting disease progression, like monoclonal antibodies.  Lifestyle interventions and occupational therapy are also available to support patients.

I believe there are reasons to hope that, despite the increasing load on the healthcare system, patient care will improve thanks to medical progress.