Biomarkers and Precision Medicine in Alzheimer’s Disease

Sagar, Ram; Pathak, P.K.; Pandur, Balint; Kim, Sujung Jun; Li, Jiaxin; Mahairaki, Vasiliki

doi:10.1007/978-3-030-78787-5_50

Cited by 6 publications

(2 citation statements)

References 42 publications

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“…Наиболее исследованной в этом плане остается болезнь Альцгеймера, где ранним биомаркером заболевания считается изменение содержания бета-амилоида-42 в ликворе, с последующим присоединением маркеров тау-патологии, изменением на МРТ и затем по-степенным когнитивным снижением по данным нейропсихологического тестирования [16]. Но персонализация доступна не только для диагностики болезни Альцгеймера, но и для выбора таргетной терапии -в том числе, с использованием человеческих индуцированных плюрипотентных стволовых клеток [17], что потенциально ускорит выделение пациентов-респондеров.…”

Section: нейродегенеративные заболеванияunclassified

Modern approaches to personalized neurology

Tanashyan

2023

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The article deals with an overview of modern concepts of personalized neurology — part of a continuum of personalized medicine. A brief historical and terminological essay is given, as well as a rationale for the importance of such an approach. Examples of promising areas of research on a wide range of biomarkers are described: biochemical, neurophysiological, angioneuroimaging, pathomorphological, etc. The issues of integrating the results of fundamental work in the field of neuroscience into clinical practice for the individualization of treatment are discussed. A general review of existing approaches to personalization in the diagnosis and therapy of the most significant neurological diseases is given: cerebrovascular pathology, epilepsy, demyelinating and neurodegenerative diseases. Future implications for the development of this area are identified and discussed, examples are described that reflect certain socio-economic aspects of personalization in neurology. The conclusion also lists a number of challenges facing this new direction in healthcare.

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Section: нейродегенеративные заболеванияunclassified

Modern approaches to personalized neurology

Tanashyan

2023

jour

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“…This uncertainty, combined with the 99% failure rate of trials of other classes of AD treatments, is rooted in an incomplete understanding of the complex mechanisms resulting in AD, and how disease trajectory and response to treatment may vary individual-to-individual. It is likely, therefore, that personalized treatment will need to play a central role in the future management and counseling of patients with AD [ 3 , 4 ]. Tailored approaches to treatment will be facilitated by the growing availability of electronic data in AD subjects and those at risk.…”

Section: Introductionmentioning

confidence: 99%

Optimal anti-amyloid-beta therapy for Alzheimer’s disease via a personalized mathematical model

2022

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With the recent approval by the FDA of the first disease-modifying drug for Alzheimer’s Disease (AD), personalized medicine will be increasingly important for appropriate management and counseling of patients with AD and those at risk. The growing availability of clinical biomarker data and data-driven computational modeling techniques provide an opportunity for new approaches to individualized AD therapeutic planning. In this paper, we develop a new mathematical model, based on AD cognitive, cerebrospinal fluid (CSF) and MRI biomarkers, to provide a personalized optimal treatment plan for individuals. This model is parameterized by biomarker data from the AD Neuroimaging Initiative (ADNI) cohort, a large multi-institutional database monitoring the natural history of subjects with AD and mild cognitive impairment (MCI). Optimal control theory is used to incorporate time-varying treatment controls and side-effects into the model, based on recent clinical trial data, to provide a personalized treatment regimen with anti-amyloid-beta therapy. In-silico treatment studies were conducted on the approved treatment, aducanumab, as well as on another promising anti-amyloid-beta therapy under evaluation, donanemab. Clinical trial simulations were conducted over both short-term (78 weeks) and long-term (10 years) periods with low-dose (6 mg/kg) and high-dose (10 mg/kg) regimens for aducanumab, and a single-dose regimen (1400 mg) for donanemab. Results confirm those of actual clinical trials showing a large and sustained effect of both aducanumab and donanemab on amyloid beta clearance. The effect on slowing cognitive decline was modest for both treatments, but greater for donanemab. This optimal treatment computational modeling framework can be applied to other single and combination treatments for both prediction and optimization, as well as incorporate new clinical trial data as it becomes available.

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