Evidence map›Paper›PMID 40844528›Full record

ArticleJournal of neurology2025

The HTT gene influences plasma neurofilament light chain and brain metabolism in prodromal Alzheimer's disease.

Salvatore Mazzeo, Chiara Crucitti, Michael Lassi, Assunta Ingannato, Valentina Berti, Matilde Nerattini, Giulia Giacomucci, Silvia Bagnoli, Valentina Moschini, Carmen Morinelli and 9 more

Abstract read
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In one paragraph

Article in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

19 authors.

Salvatore MazzeoVita-Salute San Raffaele University, Via Olgettina 58, 20132, Milan, Italy.
Chiara CrucittiDepartment of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Viale Gaetano Pieraccini, 6, 50139, Florence, Italy.
Michael LassiThe BioRobotics Institute and Department of Excellence in Robotics and AI, Scuola Superiore Sant'Anna, Viale Rinaldo Piaggio 34, Pontedera, 56025, Pisa, Italy.
Assunta IngannatoDepartment of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Viale Gaetano Pieraccini, 6, 50139, Florence, Italy.
Valentina BertiDepartment of Biomedical, Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy.
Matilde NerattiniDepartment of Biomedical, Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy.
Giulia GiacomucciResearch and Innovation Centre for Dementia-CRIDEM, Azienda Ospedaliero-universitaria Careggi, Largo Brambilla 3, 50134, Florence, Italy.
Silvia BagnoliDepartment of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Viale Gaetano Pieraccini, 6, 50139, Florence, Italy.
Valentina MoschiniResearch and Innovation Centre for Dementia-CRIDEM, Azienda Ospedaliero-universitaria Careggi, Largo Brambilla 3, 50134, Florence, Italy.
Carmen MorinelliResearch and Innovation Centre for Dementia-CRIDEM, Azienda Ospedaliero-universitaria Careggi, Largo Brambilla 3, 50134, Florence, Italy.
Sonia PadiglioniResearch and Innovation Centre for Dementia-CRIDEM, Azienda Ospedaliero-universitaria Careggi, Largo Brambilla 3, 50134, Florence, Italy.
Giulia GaldoDepartment of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Viale Gaetano Pieraccini, 6, 50139, Florence, Italy.
Filippo EmilianiDepartment of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Viale Gaetano Pieraccini, 6, 50139, Florence, Italy.
Maria SalsoneVita-Salute San Raffaele University, Via Olgettina 58, 20132, Milan, Italy.
Massimo FilippiVita-Salute San Raffaele University, and Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, IRCCS Ospedale San Raffaele, Milan, Italy.
Sandro SorbiDepartment of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Viale Gaetano Pieraccini, 6, 50139, Florence, Italy.
Alberto MazzoniThe BioRobotics Institute and Department of Excellence in Robotics and AI, Scuola Superiore Sant'Anna, Viale Rinaldo Piaggio 34, Pontedera, 56025, Pisa, Italy.
Valentina BessiResearch and Innovation Centre for Dementia-CRIDEM, Azienda Ospedaliero-universitaria Careggi, Largo Brambilla 3, 50134, Florence, Italy. valentina.bessi@unifi.it.ORCID http://orcid.org/0000-0002-6176-3584
Benedetta NacmiasDepartment of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Viale Gaetano Pieraccini, 6, 50139, Florence, Italy.

Funding

Ministero dell'Università e della Ricerca PE0000006Regione Toscana 20RSVBUniversità degli Studi di Firenze RICATEN21
6 · The paper itself

Abstract

objectiveHTT, encoding a protein involved in axonal trafficking, contains a key region of CAG repeats. When expanded beyond 39 repeats, this region leads to Huntington's disease (HD). However, several studies have suggested that increasing the number of CAG repeats below the pathological threshold may confer functional advantages by enhancing HTT activity. In the present study, we aim to investigate the association between CAG repeat length below the pathological threshold and neurodegeneration biomarkers in prodromal Alzheimer's disease (AD).

methodsNinety-five patients (36 with SCD and 59 with MCI) underwent blood collection for NfL measurement and HTT genetic analysis. Cerebrospinal fluid was collected for the measurement of Aβ₄₂, Aβ₄₀, total tau, and phosphorylated tau, and/or amyloid PET imaging was performed. Thirty-nine patients who were positive for both Aβ and phosphorylated tau biomarkers were classified as "A+/T+", while 56 patients who were either negative for both markers or positive for only one were classified as "isolated Aβ/non-AD."

resultsIn the A+/T+ group, quadratic models described the association between CAG repeat length with NfL concentrations and 18F-FDG uptake. In particular, a concave curve was observed in the medial and middle frontal gyri, while a convex curve was found in the parahippocampal and fusiform gyri.

interpretationAmong individuals with SCD and MCI who show evidence of AD pathology, CAG repeat length in the HTT gene below the HD pathological threshold is associated with biomarkers of neurodegeneration in a region-specific and U-shaped manner. These findings suggest a modulatory role of HTT in prodromal AD.

Indexed as

Alzheimer DiseaseBrainHuntingtin ProteinNeurofilament ProteinsAgedAmyloid beta-PeptidesBiomarkersCognitive DysfunctionFemaleFluorodeoxyglucose F18HumansMaleMiddle AgedPeptide FragmentsPositron-Emission TomographyProdromal SymptomsAmyloid beta-PeptidesBiomarkersFluorodeoxyglucose F18HTT protein, humanHuntingtin Proteinneurofilament protein LNeurofilament ProteinsPeptide Fragmentstau ProteinsAlzheimer’s diseaseBiomarkersBrain metabolismHuntingtonNeurofilament light chainTriplet expansions

Identifiers

PMID40844528
PMCPMC12373535

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Registered trials

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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 OpenQuestion graph.