Aug 2026· International Journal of Innovative Technologies in Social Science· Vol 1· 0 citations· 35 references
TL;DR
Plasma biomarkers offer a transformative, non-invasive approach to early AD diagnosis and primary care triage, reducing reliance on CSF and PET scans and overcoming demographic and methodological limitations is essential for their widespread clinical adoption.
Abstract
Background: Alzheimer’s disease (AD) poses major public health challenges. Traditional CSF and PET diagnostics are invasive, expensive, and limited in routine practice, driving the need for accessible plasma biomarkers.
Objectives: To evaluate the diagnostic and prognostic utility of key plasma biomarkers (plasma Aβ42/Aβ40 ratio, p-tau species, NfL, t-tau, GFAP, sTREM2) and identify limitations to their clinical implementation.
Methods: A structured literature search was conducted in the PubMed database for English-language clinical studies and review articles published between October 2007 and June 2026. Keywords and MeSH terms included "Alzheimer’s disease", "blood-based biomarkers", "immunoprecipitation-mass spectrometry (IP-MS)", and "mild cognitive impairment". Studies focusing on adult clinical biomarkers underwent a narrative synthesis.
Results: Plasma Aβ42/Aβ40 and p-tau species (p-tau181, p-tau231, p-tau217) reliably detect early amyloid pathology and differentiate AD from other dementias. NfL, GFAP, and sTREM2 track axonal damage, astrogliosis, and microglial activity, facilitating disease monitoring and therapeutic response assessment. However, clinical translation is constrained by demographic variations, somatic comorbidities, and a lack of standardized multi-marker reference ranges.
Conclusions: Plasma biomarkers offer a transformative, non-invasive approach to early AD diagnosis and primary care triage, reducing reliance on CSF and PET scans. Overcoming demographic and methodological limitations is essential for their widespread clinical adoption.
INTRODUCTION
Alzheimer's disease (AD) is a clinical-biological entity in which pathophysiological changes precede symptoms by years. Biomarkers are essential for early and accurate diagnosis, particularly in the era of disease-modifying therapies requiring biological confirmation. Cerebrospinal fluid (CSF) and amyloid positron emission tomography (amyloid-PET) are the reference standards, but increasing attention is devoted to blood-based biomarkers (BBMs) due to their scalability and cost-effectiveness.
AREAS COVERED
In this critical perspective, the authors critically appraise the current evidence supporting plasma phosphorylated tau at threonine 217 (p-tau217) as the leading BBM for AD. They also discuss its analytical performance, biological rationale, and diagnostic accuracy across the AD continuum, its relationship with established CSF, PET, and neuropathological biomarkers, its potential role in identifying patients eligible for disease-modifying therapies, and the main clinical and biological factors influencing its interpretation. Finally, they highlight current limitations, unresolved challenges, and give their future perspectives for the integration of plasma biomarkers into routine clinical practice.
EXPERT OPINION
BBMs are expected to reshape AD diagnostics. A stepwise approach, using plasma biomarkers as first-line tests followed by confirmatory CSF or PET, is currently the most feasible strategy. Ultimately, highly specific, brain-derived tau biomarkers may enable BBMs to replace CSF biomarkers.
L. Gaetani, Giovanna Nardi, Lucilla Parnetti· Expert Review of Neurotherap...· 0 citations
Background: Plasma phosphorylated tau at threonine 217 (p-tau217) has emerged as a promising minimally invasive biomarker for the biological detection of Alzheimer’s disease. This review aimed to evaluate the analytical platforms used for plasma p-tau217 measurement, their diagnostic performance, and the principal challenges associated with its implementation in clinical practice.
Methods: A structured narrative review of publications issued between 2019 and 2026 was conducted using PubMed/MEDLINE, Scopus, and Web of Science, with Google Scholar and reference-list screening used as supplementary sources. Studies evaluating plasma p-tau217 assays, analytical validation, diagnostic accuracy, comparison with positron emission tomography or cerebrospinal fluid biomarkers, and clinical implementation were included. Owing to substantial methodological and analytical heterogeneity, findings were synthesised narratively.
Results: Plasma p-tau217 showed high diagnostic performance for identifying amyloid and tau pathology and generally outperformed other phosphorylated tau isoforms. Mass-spectrometry-based measurement, particularly percentage p-tau217, demonstrated the highest analytical selectivity and diagnostic accuracy. However, fully automated immunoassays showed greater potential for routine laboratory use because of their higher throughput and reduced technical complexity. Diagnostic performance varied according to the assay, cut-off values, clinical setting, disease prevalence, and patient characteristics. A two-cut-off strategy improved classification while retaining an intermediate group requiring confirmatory testing.
Conclusions: Plasma p-tau217 may substantially improve access to biological Alzheimer’s disease diagnostics, but it should not be interpreted as a stand-alone test. Clinical implementation requires assay-specific validation, standardization, external quality control, and integration with clinical assessment and confirmatory diagnostic methods.
Oliwia Lenkiewicz, Julia Lenkiewicz, Z. Chmielewska et al.· International Journal of Inn...· 0 citations
Background. Alzheimer's disease (AD) accounts for 60–70% of the over 57 million dementia cases worldwide and is projected to nearly triple by 2050. Neuropathology precedes symptoms by roughly two decades, and the approval of anti-amyloid therapies has made biomarker-confirmed early diagnosis a clinical priority.
Aim. This narrative review synthesizes evidence on cerebrospinal fluid (CSF), blood, neuroimaging, genetic, retinal, and emerging molecular biomarkers for early detection of AD, framed within the 2024 revised NIA-AA biological criteria.
Material and methods. PubMed, MEDLINE, Google Scholar, the Journal of Education, Health and Sport, and Quality in Sport were searched for studies and consensus documents published between 2014 and 2026. Six mandatory references were integrated with seventeen additional peer-reviewed sources.
Results. CSF Aβ42/40, total tau, and p-tau181 remain reference-standard markers. Plasma p-tau217 has emerged as the leading minimally invasive biomarker, with areas under the curve of 0.92–0.96 against amyloid PET. Serum neurofilament light and glial fibrillary acidic protein support staging and differential diagnosis. Amyloid and tau PET enable in vivo Braak staging; structural MRI tracks hippocampal atrophy. APOE ε4 genotyping has regained clinical relevance in the anti-amyloid era. Optical coherence tomography, metabolomics, microRNAs, and AI-driven multimodal models expand the diagnostic frontier.
Conclusions. AD can now be detected biologically before symptoms become disabling. Translating plasma assays and AI-supported imaging into routine practice is the central challenge of the coming decade.
Aleksandra Rucka, Mateusz Kowalski, Michał Rucki et al.· Journal of Education, Health...· 0 citations
Blood-based biomarkers (BBMs) are increasingly being integrated into Alzheimer’s disease (AD) clinical pathways by providing scalable tools to track amyloid, tau, neurodegeneration, and inflammation dimensions of the ATN-I framework. As biological characterization and biomarker-informed assessment are increasingly integrated into AD care, there is growing interest in clinically applicable blood-based approaches capable of reflecting AD-related biological changes across different disease stages. This review examines recent advances in BBMs through the ATN-I framework while emphasizing their clinical decision value, analytical feasibility, economic considerations, and implementation barriers across different healthcare settings. Building on these findings, we examine the evidence supporting clinical use, with a focus on appropriate use criteria, clinical validation, laboratory feasibility, and consistent interpretation methods. Furthermore, this review explores how integrating BBMs with traditional cerebrospinal fluid and neuroimaging tests may support symptom-driven clinical triage, probability refinement, and early evaluation in selected individuals, improving clinical workflow efficiency and accessibility. Finally, the article addresses remaining challenges related to clinical validation, platform accessibility, cost-effectiveness, and equitable deployment, highlighting how emerging biomarker strategies may contribute to more scalable AD assessment.
B. Xie, Wang Zhang, Yu Zhang et al.· Frontiers in Aging Neuroscie...· 0 citations
This systematic review sought to assess the function of the blood biomarker phosphorylated tau 217 (p-tau217) in the early identification of Alzheimer's disease. A systematic review was carried out adhering to the PRISMA 2020 protocols. Literature searches were executed in PubMed, ScienceDirect, and Scopus to locate original studies published between 2023 and 2026. Eligible studies assessed blood p-tau217 in individuals with mild cognitive impairment, suspected Alzheimer's disease, Alzheimer's disease, or at-risk populations and reported diagnostic performance or correlations with established Alzheimer's biomarkers. Study quality was evaluated utilizing QUADAS-2 for diagnostic accuracy studies and the Study Quality Assessment Tools for observational and longitudinal studies. A total of 328 records were retrieved, of which 18 studies met the inclusion criteria. Research consistently demonstrates that plasma p-tau217 serves as a highly accurate biomarker for identifying the biological pathology of Alzheimer's disease, specifically regarding amyloid and tau status. Numerous studies have reported impressive area under the curve (AUC) scores between 0.92 and 0.97. When p-tau217 is paired with Aβ42 or the Aβ42/40 ratio, its diagnostic precision improves significantly, particularly in patients who are cognitively normal or in the preclinical stages of the disease.
Mangde Anata Sindhu· Health & Medical Science...· 0 citations
Over the past years, there has been an evident change in the perspective of the Alzheimer disease field where descriptive clinical diagnosis has been replaced by a biological one where molecular marker that indicate amyloid deposition, tau protein phosphorylation abnormalities, and the degree of neuron and glial damage are measured. Aβ42, Aβ40, and the Aβ42/Aβ40 ratio, as well as total tau, p-tau181, p-tau217, p-tau231, neurofilament light chain (NfL) and GFAP, the most established neurobiological markers in this area, as they connect the disease on the one hand, and the possibility of early detection, biomarker classification, and longitudinal follow-up on the other. The purpose of the review is to put these markers in a practical context based on the nature of the biological sample and the laboratory platforms to measure them, the distinctions between conventional and automated immunoassays, ultra-sensitive Simoa methods, and LC-MS/MS mass spectrometry, and to discuss the strengths and weaknesses of each method. The review also covers issues of pre-analysis, analytical validation, compatibility with the platform and derivation of cutoff values, and then considers future trends that lead to more clinically useful blood tests, such as automated tests and those that have recently undergone sophisticated regulatory review. The review finds that the real worth of these biomarkers is not just in their availability but also in choosing the right biomarker to the right clinical question and in maintaining the integrity of the measurement chain between sample collection and interpreting the results.
Mustafa Alburhan, Abdulla Munthir Sulaiman, Bakr Aldoori· Libyan Journal of Applied an...· 0 citations