Evidence map›Paper›PMID 42196496›Full record

ReviewInternational journal of molecular sciences2026

Analytical Methods for Fluid Biomarkers in Alzheimer's Disease from Discovery to Clinical Implementation.

Luisa Agnello, Roberto Dominici, Caterina Maria Gambino, Concetta Scazzone, Marcello Ciaccio

Abstract readReview
In one paragraph

Review in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Luisa AgnelloDepartment of Biomedicine, Neurosciences, and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy.
Roberto DominiciUniversity Laboratory of Clinical Pathology and Toxicology, Pio XI Hospital, Desio, ASST Brianza, 20832 Desio, Italy.ORCID 0000-0003-0280-6238
Caterina Maria GambinoDepartment of Biomedicine, Neurosciences, and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy.
Concetta ScazzoneDepartment of Biomedicine, Neurosciences, and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy.ORCID 0000-0001-7424-8066
Marcello CiaccioDepartment of Biomedicine, Neurosciences, and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy.ORCID 0000-0001-6120-9041

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) is increasingly recognized as a biological continuum characterized by early neuropathological and molecular changes that precede the onset of clinical symptoms. Fluid biomarkers have transformed the diagnostic landscape by enabling the in vivo detection of core AD pathologies, particularly amyloid-β deposition and tau-related neurodegeneration. Despite the rapid expansion of candidate biomarkers, however, only a limited number have successfully translated into clinical practice. Discovery-phase approaches, primarily driven by mass spectrometry-based proteomics, enable the unbiased identification of novel biomarker candidates across multiple biological pathways. Research-phase methods, including immunoassays such as enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence immunoassays (ECLIA), microfluidic platforms, and ultrasensitive technologies such as single-molecule array (SIMOA), support analytical and clinical validation in well-characterized cohorts. Clinical implementation has been advanced by fully automated platforms, including Lumipulse and Elecsys, which have obtained regulatory approval for cerebrospinal fluid biomarkers and, more recently, blood-based biomarkers. These developments represent a paradigm shift toward minimally invasive and scalable diagnostic strategies that may reduce dependence on neuroimaging techniques. Nevertheless, major challenges remain, including assay standardization, inter-platform variability, demonstration of clinical utility, and barriers to widespread clinical adoption. This review provides a comprehensive overview of analytical methods used to measure AD fluid biomarkers in cerebrospinal fluid and plasma, structured according to the biomarker development pipeline from discovery to clinical implementation. Overall, the review highlights a fit-for-purpose approach to biomarker development and emphasizes the complementary roles of diverse analytical technologies across the different phases of biomarker translation.

Indexed as

Alzheimer DiseaseBiomarkersAmyloid beta-PeptidesAnimalsEnzyme-Linked Immunosorbent AssayHumansImmunoassayProteomicstau ProteinsAmyloid beta-PeptidesBiomarkerstau ProteinsAlzheimer’s diseasebiofluidsbiomarkersbloodCSFdiscoveryFDA

Identifiers

PMID42196496
PMCPMC13206942

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.