Evidence mapPaperPMID 41495835Full record

ArticleAlzheimer's research & therapy2026

Plasma extracellular vesicles and phosphorylated tau 181 as early biomarkers of cognitive impairment in Alzheimer's dementia.

Viviana Brembati, Daniela Crescenti, Andrea Geviti, Elisa Rossini, Federico Angelo Cazzaniga, Fabio Moda, Elisa R Zanier, Gisella Guerrera, Luca Battistini, Simone Baiardi and 37 more

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Article in Alzheimer's research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
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

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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

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
4 · The record

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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

47 authors.

Viviana Brembati *Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, 25125, Italy.
Daniela Crescenti *Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, 25125, Italy. dcrescenti@fatebenefratelli.eu.
Andrea GevitiService of Statistics, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, 25125, Italy.
Elisa RossiniMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, 25125, Italy.
Federico Angelo CazzanigaUnit of Laboratory Medicine - Laboratory of Clinical Pathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, 20133, Italy.
Fabio ModaUnit of Laboratory Medicine - Laboratory of Clinical Pathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, 20133, Italy.
Elisa R ZanierDepartment of Acute Brain and Cardiovascular Injury, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Milan, 20156, Italy.
Gisella GuerreraNeuroimmunology Unit, IRCCS Santa Lucia Foundation, Rome, 00179, Italy.
Luca BattistiniNeuroimmunology Unit, IRCCS Santa Lucia Foundation, Rome, 00179, Italy.
Simone BaiardiIRCCS Istituto Delle Scienze Neurologiche Di Bologna, Bologna, Italy.
Alessandra MandelliClinical Neuroimmunology Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milan, 20132, Italy.
Roberto FurlanClinical Neuroimmunology Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milan, 20132, Italy.
Federico VerdeDepartment of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, 20149, Italy.
Benedetta NacmiasIRCCS Fondazione Don Carlo Gnocchi, Florence, 50143, Italy.
Chiara Adriana EliaNeuroscience Institute, Consiglio Nazionale Ricerche, URT C/O IRCCS Humanitas Research Hospital, Rozzano, 20089, Italy.
Maria Luisa MalosioNeuroscience Institute, Consiglio Nazionale Ricerche, URT C/O IRCCS Humanitas Research Hospital, Rozzano, 20089, Italy.
Alberto ImarisioNeurogenetics Research Centre, IRCCS Mondino Foundation, Pavia, 27100, Italy.
Franca Rosa GueriniIRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, 20148, Italy.
Chiara FenoglioIRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Milan, 20122, Italy.
Alessio Di FonzoIRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Milan, 20122, Italy.
Leonardo BiscettiSection of Neurology, Italian National Research Center On Aging (IRCCS INRCA), Ancona, 60121, Italy.
Margherita SquillarioLISCOMP Laboratory, IRCCS Ospedale Policlinico San Martino, Genoa, 16132, Italy.
Silvia BerraLISCOMP Laboratory, IRCCS Ospedale Policlinico San Martino, Genoa, 16132, Italy.
Francesca MiragliaBrain Connectivity Laboratory, Department of Neuroscience and Neurorehabilitation, IRCCS San Raffaele Roma, Rome, 00166, Italy.
Paolo Maria RossiniDepartment of Neuroscience & Neurorehabilitation, IRCCS San Raffaele Roma, Rome, 00163, Italy.
Camillo MarraNeurology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, 00168, Italy.
Nicola VanacoreNational Center for Disease Prevention and Health Promotion, National Institute of Health, Rome, 00161, Italy.
Alberto RedolfiLaboratory of Neuroinformatics, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, 25125, Italy.
Daniela PeraniVita-Salute San Raffaele University, Milan, 20132, Italy.
Patrizia SpadinAssociazione Italiana Malattia Di Alzheimer - AIMA, Milan, 20149, Italy.
Maria CotelliNeuropsychology Unit, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, 25125, Italy.
Stefano CappaUniversity Institute of Advanced Studies (IUSS-Pavia), Pavia, 27100, Italy.
Naike CaragliaMemory Clinic, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, 00168, Italy.
Fabrizio VecchioBrain Connectivity Laboratory, Department of Neuroscience and Neurorehabilitation, IRCCS San Raffaele Roma, Rome, 00166, Italy.
Pietro TiraboschiFondazione IRCCS Istituto Neurologico Carlo Besta, Milan, 20133, Italy.
Federica PirasLaboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, 00179, Italy.
Giovanni B FrisoniGeneva Memory Center, Geneva University Hospitals, Geneva, 1205, Switzerland.
Cristina MuscioFondazione IRCCS Istituto Neurologico Carlo Besta, Milan, 20133, Italy.
Raffaele LodiIRCCS Istituto Delle Scienze Neurologiche Di Bologna, Bologna, Italy.
Piero ParchiIRCCS Istituto Delle Scienze Neurologiche Di Bologna, Bologna, Italy.
Fabrizio TagliaviniFondazione IRCCS Istituto Neurologico Carlo Besta, Milan, 20133, Italy.
Enza Maria ValenteNeurogenetics Research Centre, IRCCS Mondino Foundation, Pavia, 27100, Italy.
Gianluigi ForloniDepartment of Neuroscience, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Milan, 20156, Italy.
Roberta GhidoniMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, 25125, Italy. rghidoni@fatebenefratelli.eu.
INTERCEPTOR Network
Network-AD project
Biomarker Italian Team

Funding

Italian Ministry of Health RCR-2021-23671214Italian Ministry of Health RCR-2022-23682291
6 · The paper itself

Abstract

backgroundTimely and accurate diagnosis of Alzheimer’s disease (AD) in clinical practice is a great challenge, especially during early disease stages with subtle or mild symptoms of cognitive decline. Moreover, robust and more accessible blood-based screening tests for early diagnosis are needed. In this study, we investigated the core AD blood biomarkers — amyloid beta 42 (Aβ42) and 40 (Aβ40) peptides, phosphorylated tau 181 (p-Tau181), neurofilament light chain (NfL), and total tau (t-Tau) — and extracellular vesicle (EVs) size and concentration in individuals characterized by different stages of cognitive decline to identify biochemical markers of dementia for early diagnosis.

methodsA total of n = 800 human plasma samples were analyzed. Plasma levels of NfL, t-Tau, p-Tau181, Aβ42, Aβ40 and plasma EVs were evaluated in n = 217 elderly healthy subjects (CTRL), in individuals with subjective cognitive complaints (SCC, n = 48), pre-mild cognitive impairment (pre-MCI, n = 58) and mild cognitive impairment (MCI, n = 426), and in n = 51 probable AD dementia patients (AD-dem), using ultrasensitive Single Molecule Array technology (Simoa®) and nanoparticle tracking analysis (NTA). Logistic regression and Receiver Operating Characteristic (ROC) analyses were employed.

resultsPlasma NfL displayed increased levels in AD-dem and MCI patients, while p-Tau181, Aβ42/Aβ40 ratio, Aβ42/p-Tau181 ratio, and EVs plasma levels were altered since the early stages of the pathology: in particular, p-Tau181 levels increased as cognitive symptoms worsened, already in the SCC and pre-MCI groups compared to CTRL, while the ratio of EVs concentration and size (EVs ratio) was decreased in all groups compared to CTRL. Plasma p-Tau181 best classified AD-dem patients from CTRL with an area under the curve (AUC) equal to 0.87, while EVs ratio best differentiated SCC from CTRL (AUC = 0.78). Combining p-Tau181 and EVs ratio with Aβ42/Aβ40 ratio and NfL, respectively, significantly improved the classification of pre-MCI and MCI from CTRL (AUCcomb = 0.79 and AUCcomb = 0.85). Combining biomarkers did not improve accuracy in discriminating MCI from SCC, pre-MCI and AD-dem.

conclusionsp-Tau181 and EVs ratio are promising biomarkers for the identification of individuals at risk of degenerative dementia. Combining the core AD plasma biomarkers with EVs ratio can aid in diagnosing the early stages of AD dementia.

Indexed as

Alzheimer DiseaseCognitive DysfunctionExtracellular Vesiclestau ProteinsAgedAged, 80 and overAmyloid beta-PeptidesBiomarkersFemaleHumansMaleNeurofilament ProteinsPeptide FragmentsPhosphorylationROC CurveAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)BiomarkersMAPT protein, humanNeurofilament ProteinsPeptide Fragmentstau ProteinsAlzheimer’s dementiaAmyloid beta peptideEarly diagnosisExtracellular vesiclesMild cognitive impairmentNeurofilament lightPhosphorylated Tau 181Plasma biomarkersPreclinical stagesUltrasensitive assays

Identifiers

PMID41495835
PMCPMC12777469

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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 Socratic graph.