. Scientific Frontline: Lack of biomarker profiles typical of Alzheimer's disease

Monday, October 17, 2022

Lack of biomarker profiles typical of Alzheimer's disease

Image credit: Gerd Altmann

A new study from Karolinska Institutet and Karolinska University Hospital shows that only a small proportion of patients who were examined for cognitive illness at the specialized memory reception at Karolinska Hospital in Solna had biomarker profiles typical of Alzheimer's disease and could be considered as potential candidates for new disease-modifying treatments. against amyloid.

This study was done in collaboration between Karolinska Institutet and Janssen Pharmaceutica NV (part of Janssen Pharmaceutical Companies of Johnson & Johnson), and was published online in the journal Neurology, the medical journal of the American Academy of Neurology.

Biomarkers that reflect typical changes in brain pathology in Alzheimer's disease are an important support in the diagnosis, as well as finding which patient group is suitable for which new disease-modifying treatment, when such drugs become available in the market. At present, however, there is only limited data on the proportion of patients in regular clinics and memory clinics (ie who are not participants in research studies) who have Alzheimer's-type biomarkers and who could thus be the right patient group for these new drugs.

Large patient base at the Solna memorial reception

In this study, the research team led by Professor Miia Kivipelto, MD PhD, has examined biomarker profiles in a well-characterized patient group at the memorial reception at Karolinska University Hospital in Solna. The clinical investigation process at the newly started clinic (which opened in 2018) has given rise to a large amount of well-documented information. The memory reception receives patients with memory problems from primary care in the reception area as well as younger patients under 70 years from the entire Stockholm region. The investigation process follows a "fast track model" where a majority of all investigations are done within a week. Most patients undergo lumbar puncture for spinal cord fluid collection, magnetic camera examination of the brain, and most neuropsychological tests. These survey results are then compiled into a diagnosis. All patients are also asked for permission to participate in the hospital's research database and biobank (GEDOC).

The memorial reception in Solna is a good example of a clinic with the opportunity and resources for highly specialized diagnostic investigations and for implementing the future of new treatments for Alzheimer's disease. In this study, biomarkers were examined based on the so-called ATN model, and the purpose was to understand the proportion of patients who had abnormal biomarkers for amyloid (A), tau (T), and neurodegenerative changes (N) which are typical findings in Alzheimer's disease. . Based on these biomarkers and the clinical patient data collected, the research team also investigated how large a proportion of patients would potentially be suitable for new disease-modifying drugs for amyloid. Anti-amyloid drugs are the first group of new Alzheimer's drugs that have been approved (in the United States) for use, and in this study the US criteria for assessing suitability were used. The study included all patients on the reception from opening to February 2021 who gave consent to research participation (N = 410; 52% with a diagnosis of subjective memory disorder, 23% for mild cognitive disorder, 25% with dementia; mean age 59).

Most had normal biomarkers

The research team discovered that most patients in the study had normal biomarker profiles, ie none of the biomarkers studied were considered deviant. This applied to both traditional limit values used in the laboratory and more permissible data-driven limit values developed in the study. Depending on the limit values used, up to 30% of patients had abnormal amyloid values (17% based on laboratory limit values) which is less than previously reported. Based on the criteria for anti-amyloid treatment based on biomarkers and health and cognitive status, only 13% of patients were currently potential candidates for treatment. Even in those with mild cognitive disorder or dementia, only about a quarter of patients were possible candidates for treatment. Since the research team could not evaluate all relevant exclusion criteria, the actual proportion that would in practice be offered treatment may be even lower.

This study shows that at a highly specialized memory reception with good investigative resources and opportunities to introduce new treatments for Alzheimer's disease, most patients would probably not be candidates for the new anti-amyloid drugs. The study shows that further development of disease-modifying treatments is needed in addition to the anti-amyloid alternatives. By using the information from the GEDOC research database which includes extensive clinical information as well as a linked biobank, the researchers in the team hope to learn more about the diversity of Alzheimer's disease and cognitive failure as well as the underlying mechanisms for this.

This study was supported by EU JPND (EURO FINGERS) Alzheimer's Foundation, Swedish Research Council, Stockholm Region, CIMED (Karolinska Institutet) Stockholm Hospital Foundation, Knut and Alice Wallenberg Foundation, King Gustaf V's and Queen Victoria's Freemason Foundation, EU / EFPIA Innovative Medicines Initiative Joint Undertaking (EPAD) European Research Council, and Academy of Finland.

Source/Credit: Karolinska Institutet

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