Today, the World Health Organization (WHO) published the preferred product characteristics (PPC) of blood-based biomarker diagnostics for Alzheimer disease (AD) . The PPC aims to inform the development of blood-based biomarker diagnostics (tests) for AD by ensuring that tests achieve optimal clinical performance and will be suitable for future use in a range of settings including low- and middle-income countries (LMICs).
The primary audience for this PPC includes entities intending to eventually seek WHO policy recommendations and prequalification. It offers guidance to funders, researchers, product developers and regulatory agencies in the development and implementation of diagnostic tools using blood-based biomarkers for AD.
Realizing the potential of blood-based biomarkers for AD diagnosis
Dementia is a major cause of disability and the seventh leading cause of death globally. In 2019, over 55 million people were estimated to be living with dementia, of which 60–70% were caused by AD.
Receiving a timely and accurate AD diagnosis is a prerequisite for accessing services and support for the person, families and care partners.
Currently, a diagnosis of AD is based on clinical judgment, which can be supported by imaging techniques and laboratory analysis of cerebrospinal fluid (CSF). However, there is a global shortage of qualified health professionals and access to imaging and CSF analysis is similarly limited, particularly LMICs, where the number of specialized healthcare workforce is low.
Scientific evidence on the use of blood-based biomarkers to support the diagnosis of AD has shown promising advances in recent years, including improved assay sensitivity and specificity, potential for earlier detection of Alzheimer's disease in preclinical stages and high diagnostic accuracy in distinguishing AD from all other neurodegenerative diseases in people with cognitive impairment.
The use of blood-based biomarkers therefore has enormous potential to support health systems in improving the diagnosis of AD. This is especially relevant in settings where the size of the specialized healthcare workforce is significantly low and health system infrastructure and funding are unable to provide specialized neurological services sustainably to populations.
Developing accessible and equitable diagnostic tools
Current AD blood tests are being studied in highly resourced, carefully controlled clinical settings, often involving populations with limited diversity. The real-world implementation of AD blood tests requires further validation on a larger scale, with diverse populations and considering the clinical contexts in which they will be utilized. This is particularly relevant in the case of LMICs, which is where the expected global increase in dementia prevalence is expected to happen.
The PPC therefore defines a range of characteristics to promote the development of future diagnostic products that will exhibit appropriate features that are relevant for the intended context of use.
The PPC specify the intended use and target population for these tests and outlines its desired clinical performance. It also emphasizes the importance of providing guidance on how to interpret results, which must consider factors such as age, sex, genetic mutations, medications, comorbidities, local/regional conditions and disease stage. Additionally, the PPC highlights key aspects that need to be considered, including accessibility, affordability, workforce capacity and training, requirements of technical support and equipment maintenance.
The PPC also highlights, in line with the WHO's global dementia action plan , the importance of pairing diagnostic tools with increased access to post-diagnostic support, as well as the participation and empowerment of people with lived experience in the development process of such tests.
Overview of the PPC development process
The PPC was developed in line with WHO Target product profiles, preferred product characteristics, and target regimen profiles: standard procedure, second edition, 2024. The preferred parameters of blood-based biomarker diagnostics for AD were developed in collaboration with the PPC Development Group, consisting of 20 leading scientists and experts. Between April and May 2024, a draft of the PPC was posted online for public consultation . A total of 18 individuals or organizations submitted comments. Inputs were discussed with the Development Group and revisions to the PPC were made when appropriate and relevant.
People living with dementia were involved in the development of this PPC. Their recommendations are included in the document and highlight the importance of taking account of the perspective of people with lived experience to ensure suitability and uptake.
