Use of Biomarkers in Ongoing Research Protocols on Alzheimer’s Disease

Canevelli, Marco; Remoli, Giulia; Bacigalupo, Ilaria; Valletta, Martina; Blasi, Marco Toccaceli; Sciancalepore, Francesco; Bruno, Giuseppe; Cesari, Matteo; Vanacore, Nicola

doi:10.3390/jpm10030068

Cited by 10 publications

(3 citation statements)

References 28 publications

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“…The validation of a biomarker used to identify pathology requires knowledge of its distribution in healthy individuals and therefore of a reference group. Individual characteristics that should be considered include ethnicity, sex, clinical history, and frailty, as these could have significant impact on the expression of pathology [ 36 ].…”

Section: Resultsmentioning

confidence: 99%

Lights and Shadows of Cerebrospinal Fluid Biomarkers in the Current Alzheimer’s Disease Framework

Gallucci

Cenesi

White

et al. 2022

JAD

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Background: The most significant biomarkers that are included in the Alzheimer’s disease (AD) research framework are amyloid-β plaques deposition, p-tau, t-tau, and neurodegeneration. Although cerebrospinal fluid (CSF) biomarkers are included in the most recent AD research criteria, their use is increasing in the routine clinical practice and is applied also to the preclinical phases of AD, including mild cognitive impairment. The role of these biomarkers is still unclear concerning the preclinical stage of AD diagnosis, the CSF methodology, and the costs-benefits of the biomarkers’ tests. The controversies regarding the use of biomarkers in the clinical practice are related to the concepts of analytical validity, clinical validity, and clinical utility and to the question of whether they are able to diagnose AD without the support of AD clinical phenotypes. Objective: The objective of the present work is to expose the strengths and weaknesses of the use of CSF biomarkers in the diagnosis of AD in a clinical context. Methods: We used PubMed as main source for articles published and the final reference list was generated on the basis of relevance to the topics covered in this work. Results: The use of CSF biomarkers for AD diagnosis is certainly important but its indication in routine clinical practice, especially for prodromal conditions, needs to be regulated and also contextualized considering the variety of possible clinical AD phenotypes. Conclusion: We suggest that the diagnosis of AD should be understood both as clinical and pathological.

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Section: Resultsmentioning

confidence: 99%

Lights and Shadows of Cerebrospinal Fluid Biomarkers in the Current Alzheimer’s Disease Framework

Gallucci

Cenesi

White

et al. 2022

JAD

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“…The current role of biomarkers in AD clinical trial is to ensure appropriate patient selection, intercepting subjects in the Alzheimer s continuum [9]. The demonstration of targeted engagement seems to be crucial; however, less than 60% of current trials relies on it [133]. On the other hand, each of the proposed trials enrolled patients with evidence of amyloid pathology (PET or CSF detection) in different clinical stages of disease (prodromal, early symptomatic, mild AD).…”

Section: Admentioning

confidence: 99%

Fluid Biomarkers in Alzheimer’s Disease and Other Neurodegenerative Disorders: Toward Integrative Diagnostic Frameworks and Tailored Treatments

et al. 2022

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The diagnosis of neurodegenerative diseases (NDDs) represents an increasing social burden, with the unsolved issue of disease-modifying therapies (DMTs). The failure of clinical trials treating Alzheimer′s Disease (AD) so far highlighted the need for a different approach in drug design and patient selection. Identifying subjects in the prodromal or early symptomatic phase is critical to slow down neurodegeneration, but the implementation of screening programs with this aim will have an ethical and social aftermath. Novel minimally invasive candidate biomarkers (derived from blood, saliva, olfactory brush) or classical cerebrospinal fluid (CSF) biomarkers have been developed in research settings to stratify patients with NDDs. Misfolded protein accumulation, neuroinflammation, and synaptic loss are the pathophysiological hallmarks detected by these biomarkers to refine diagnosis, prognosis, and target engagement of drugs in clinical trials. We reviewed fluid biomarkers of NDDs, considering their potential role as screening, diagnostic, or prognostic tool, and their present-day use in clinical trials (phase II and III). A special focus will be dedicated to novel techniques for the detection of misfolded proteins. Eventually, an applicative diagnostic algorithm will be proposed to translate the research data in clinical practice and select prodromal or early patients to be enrolled in the appropriate DMTs trials for NDDs.

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“…It is not surprising that the most of papers are addressed to review the current knowledge about biomarkers detected in different biological fluids, which are mainly related to pathophysiological processes occurring in AD (e.g., vascular dysfunction, neuroinflammation, and synaptic and neuronal integrity). These reviews largely describe and discuss potential biomarkers detected in CSF or blood as well as in alternative non-invasive body fluids and their possible use in early diagnosis [ 3 , 4 , 5 , 6 , 7 ] or ongoing research protocols on AD [ 8 ]. Among them, an emerging role of flotillin as promising biomarker for AD has been proposed by some authors [ 9 ].…”

mentioning

confidence: 99%