Role of Biomarkers for the Diagnosis of Prion Diseases: A Narrative Review

Abstract

Prion diseases are progressive and irreversible neurodegenerative disorders with a low incidence (1.5–2 cases per million per year). Genetic (10–15%), acquired (anecdotal) and sporadic (85%) forms of the disease have been described. The clinical spectrum of prion diseases is very varied, although the most common symptoms are rapidly progressive dementia, cerebellar ataxia and myoclonus. Mean life expectancy from the onset of symptoms is 6 months. There are currently diagnostic criteria based on clinical phenotype, as well as neuroimaging biomarkers (magnetic resonance imaging), neurophysiological tests (electroencephalogram and polysomnogram), and cerebrospinal fluid biomarkers (14-3-3 protein and real-time quaking-induced conversion (RT-QuIC)). The sensitivity and specificity of some of these tests (electroencephalogram and 14-3-3 protein) is under debate and the applicability of other tests, such as RT-QuIC, is not universal. However, the usefulness of these biomarkers beyond the most frequent prion disease, sporadic Creutzfeldt–Jakob disease, remains unclear. Therefore, research is being carried out on new, more efficient cerebrospinal fluid biomarkers (total tau, ratio total tau/phosphorylated tau and neurofilament light chain) and potential blood biomarkers (neurofilament light chain, among others) to try to universalize access to early diagnosis in the case of prion diseases.

Exploring the Potential of Biomarkers for Early Diagnosis and Management of Sporadic Creutzfeldt - Jakob disease; A Review

“…Therefore, identifying biomarkers for diagnosing and managing sCJD is critical. Among the biomarkers investigated, protein biomarkers such as 14-3-3 protein and tau protein have been extensively studied due to their ability to reflect the neuronal damage associated with sCJD (5,6). Imaging biomarkers, including magnetic resonance imaging (MRI) and positron emission tomography (PET) scans, have also been investigated for their potential use in sCJD diagnosis and management (7).…”

Prion diseases disrupt the glutamate/glutamine metabolism in skeletal muscle

“…Clinical trials of investigational new drugs require easily accessible and highly specific biomarkers, yet prion replication in brain cannot be assessed non-invasively. Cyclical prion seed amplification can sensitively detect PrP Sc in cerebrospinal fluid (CSF) (Altuna Azkargorta et al, 2022; Hermann et al, 2021) and nasal swab samples (Behaeghe et al, 2018; Di Fede et al, 2018), but variations in sample preparation, equipment, and interpretation criteria can lead to inconsistent results and reduce its reproducibility (Bongianni et al, 2017; Orrú et al, 2017). Moreover, these techniques can generate false-positive results due to the detection of other amyloidogenic proteins, such as Aβ, α-synuclein, and tau (Cramm et al, 2016) and their sensitivity may be influenced by the strain of prions, the stage of disease and the tissue source used for the assay (Cramm et al, 2016; Hermann et al, 2021).…”

Biomarkers in Alzheimer Disease and Other Dementias: What’s Next into Pathophysiology to Support Clinical Practice and Drug Development

“…Prion diseases are rare, irreversible neurodegenerative disorders with rapidly progressive dementia, cerebellar ataxia and myoclonus. Altuna et al [ 7 ] reviewed current neuroimaging, neurophysiological and CSF biomarkers (14-3-3 protein and real-time quaking-induced conversion (RT-QuIC)). The sensitivity and specificity of some of these tests (electroencephalogram and 14-3-3 protein) areunder debate, and the applicability of other tests, such as RT-QuIC, is not universal.…”

“…The sensitivity and specificity of some of these tests (electroencephalogram and 14-3-3 protein) areunder debate, and the applicability of other tests, such as RT-QuIC, is not universal. However, Altuna et al [ 7 ] doubted the usefulness of these biomarkers beyond the most frequent prion disease, sporadic Creutzfeldt–Jakob disease, and further investigations are warranted.…”