Alzheimer’s disease, biomarkers, and the future of biology-based diagnoses

 In Alzheimer's Disease

Medical technology evolves rapidly, but many healthcare professionals continue to use outdated and one-dimensional diagnostic tools. These often fail to detect neurological conditions like Alzheimer’s disease in their early stages, preventing life-changing intervention and treatment.

In this article, I’ll discuss my clinic’s research into new diagnostic tools and treatments that leverage biomarkers to facilitate early detection and patient-tailored care.

Searching for targeted and effective treatments

Over the past six years, about 50 percent of the studies at my clinic, Sharlin Health Neuroscience Research Center, have involved a special type of antibody called therapeutic monoclonal antibodies.

Antibodies are Y-shaped proteins that lock on like puzzle pieces to another type of protein called antigens. Antibodies circulate throughout the body until they find and attach to the correct antigen, acting like the immune system’s search-and-destroy battalion.

Researchers in my team design antibodies that target particular antigens, such as one that identifies a specific type of B-cell or an over-active immune cell in multiple sclerosis (MS), or one that helps to clear amyloid-beta from the brain in Alzheimer’s disease.

This research asks big questions about the potential of these targeted therapies in the treatment of supposedly untreatable neurological diseases, including:

  • How can we create highly targeted therapies using monoclonal antibodies?
  • How will the body’s immune system react to these treatments? Will it neutralize the antibodies before they can take effect? Will the effect plateau over time?
  • Should treatments be tailored to the biological uniqueness of each person affected by a given condition? Can treatments be personalized in this way?

The role of biomarkers in our research

To answer these types of questions, we often turn to biomarkers. Short for “biological marker,” this term refers to objective, quantifiable characteristics of biological processes.

Biomarkers include the following:

  • Diagnostic biomarkers are used to confirm the diagnosis. Diagnostic biomarkers may facilitate earlier detection of a disorder than can be achieved by other approaches.
  • Prognostic biomarkers help to indicate how a disease may develop in an individual when a disorder is already diagnosed. The presence or absence of a prognostic marker can be helpful in the selection of patients for treatment but does not directly predict the response to treatment.
  • Predictive biomarkers help to determine which patients are most likely to benefit from a specific treatment option. Predictive diagnostics can provide information about how well a treatment is likely to work in a particular patient or about the likelihood of that treatment causing an unwanted side effect. These biomarkers are used for prognosis and prediction.
  • Disease activity biomarkers consist of biomarkers that measure the inflammatory and/or neurodegenerative components of the disease.
  • Treatment-response biomarkers help to differentiate patients regarding their outcome related to efficacy and side effects (treatment responders and non-responders as well as patients with and without adverse drug reactions). In addition, these treatment-response markers could be applicable for all treatments or be tailored to a specific treatment only.

Conventional diagnostic tools, biomarkers, and Alzheimer’s disease

To help you better understand the value of biomarkers in our research and the diagnosis of patients, let’s walk through an example.

Meet Jim. Jim is a 66-year-old gentleman who, over the past few years, has started to struggle with word-finding, complete thoughts in conversation, and follow-through on tasks. He has even done things that presented a safety concern around his grandchildren.

Jim has a family history of dementia. He underwent an MRI of the brain that showed age-related changes but otherwise appeared normal and healthy. His routine blood work was normal. Two weeks ago, his Montreal Cognitive Assessment(MoCA) – a screening test designed to aid healthcare professionals in the identification of cognitive impairments and Alzheimer’s – was a perfect 30/30.

Does Jim have Alzheimer’s disease?

First, let’s look at the 1984 Clinical Diagnostic Criteria for PROBABLE Alzheimer’s Disease

  • Dementia
  • Deficits in two or more areas of cognition
  • Progressive worsening of memory and other cognitive functions
  • No disturbance of consciousness
  • Onset between ages 40 and 90, most often after age 65
  • Absence of systemic disorders or other brain diseases that in and of themselves could account for the progressive decline in memory and cognition

Although the criteria were updated in 2011, recommendations relating to pre-clinical diagnoses are “intended purely for research purposes.”

Many clinics today use these symptom-based criteria to diagnose Alzheimer’s disease. If our patient Jim were to walk into one of those clinics, he would not be diagnosed with Alzheimer’s, and he would not be offered treatment.

To me, that is not good enough, and that’s why I turn to biomarkers.

Moving toward a biological definition of Alzheimer’s disease

Alzheimer’s is not switched on like a light. It exists on a continuum. The pre-clinical state can last for one to two decades before the disease manifests to the point that we could use conventional diagnostic tools to call it mild cognitive impairment (MCI) or dementia due to Alzheimer’s disease.

At my clinic, I look beyond symptom-based criteria toward a biological definition of Alzheimer’s disease that uses biomarkers to help inform a pre-clinical diagnosis.

For example, I use spinal fluid examinations to detect amyloid protein or beta-amyloid 42, tau protein, and phosphorylated tau. 

Beta-amyloid protein indicates inflammation – when your brain and body have inflammatory threats, your amyloid levels increase. In those with Alzheimer’s disease, amyloid creates an insoluble protein that, over time, builds up, causes nerve cells to break down, and triggers the release of a protein called tau. 

Once the burden of beta-amyloid protein has reached a certain threshold, then we start to see the buildup of a second protein – “tau” – which comes from the insides of nerve cells. The tau protein normally functions as part of the system which transports substances down the long arm of the nerve cell called the axon. When nerve cells are destroyed, tau is released into the brain and the spinal fluid where it can be measured. Perhaps it is not a surprise that the more nerve cell destruction, the worse the cognitive decline. It might also make sense that we should try to identify the person at risk for Alzheimer’s disease before there is a large build of tau, in other words, before significant nerve cell destruction. 

Using the data from a spinal fluid exam, I plot a calculation called the amyloid-tau index against the level of phosphorylated tau. If the results land above the cut-off point, the biomarkers are consistent with Alzheimer’s disease.

This biology-based approach to diagnosis can help me catch the disease in its infancy and allow for early intervention and treatment. With further research into the potential of therapeutic monoclonal antibodies, perhaps Alzheimer’s could be reversed or prevented altogether.

Now, we can go back to Jim. Using tests that target specific biomarkers, I was able to identify the degree of the build-up of amyloid and tau proteins. In what might seem like the medicine of tomorrow, we can give Jim a more accurate diagnosis of early, evolving Alzheimer’s disease, based on the presence of biomarkers, and take steps, using biological therapy and the principles of functional medicine which addresses the causes of inflammation, to offer the possibility of Alzheimer’s disease reversal and hope for the future.  

Experience the future of neurology today

If you’d like to learn more about my leading-edge approach to neurology or become a patient at my clinic, please do not hesitate to schedule a consultation today.

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