Replication of blood DNA methylomic signatures associated with cerebrospinal fluid levels of YKL-40 and NfL biomarkers

Timo Kaleck; Rafael Campos-Martin; Amanda Cano; Maria Victoria Fernández; Pamela Martino-Adami; Luca Kleineidam; Victor M.Andrade Fuentes; Kumar P. Tripathi; Kayenat Parveen; Raquel Puerta; Itziar de Rojas; Kishore A. Ravichandran; Oliver Peters; Julian Hellmann-Regen; Josef Priller; Maria Gemenetzi; Anja Schneider; Jens Wiltfang; Emrah Düzel; Katharina Buerger; Robert Perneczky; Stefan Teipel; Christoph Laske; Frederic Brosseron; Marta Marquié; Daniel L.A. van den Hove; Mercè Boada; Michael T. Heneka; Michael Wagner; Natalie Marchant; Jean Charles Lambert; Ruth Frikke-Schmidt; Frank Jessen; Agustín Ruiz; Alfredo Ramirez

doi:10.1002/alz.70647

Replication of blood DNA methylomic signatures associated with cerebrospinal fluid levels of YKL-40 and NfL biomarkers

Timo Kaleck
, Rafael Campos-Martin
, Amanda Cano
, Maria Victoria Fernández
, Pamela Martino-Adami
, Luca Kleineidam
, Victor M.Andrade Fuentes
, Kumar P. Tripathi
, Kayenat Parveen
, Raquel Puerta
, Itziar de Rojas
, Kishore A. Ravichandran
, Oliver Peters
, Julian Hellmann-Regen
, Josef Priller
, Maria Gemenetzi
, Anja Schneider
, Jens Wiltfang
, Emrah Düzel
, Katharina Buerger

Robert Perneczky, Stefan Teipel, Christoph Laske, Frederic Brosseron, Marta Marquié, Daniel L.A. van den Hove, Mercè Boada, Michael T. Heneka, Michael Wagner, Natalie Marchant, Jean Charles Lambert, Ruth Frikke-Schmidt, Frank Jessen, Agustín Ruiz, Alfredo Ramirez^*

^*Corresponding author for this work

Research output: Contribution to journal › Comment/Letter to the editor › Academic › peer-review

Original language	English
Article number	e70647
Number of pages	4
Journal	Alzheimer's & Dementia
Volume	21
Issue number	9
DOIs	https://doi.org/10.1002/alz.70647
Publication status	Published - 1 Sept 2025

Keywords

Alzheimer's disease (AD)
amyloid
biomarker
blood
cerebrospinal fluid (CSF)
DNA methylation
epigenetics
epigenome-wide association study (EWAS)
neurofilament light (NfL)
ptau
replication
YKL-40

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10.1002/alz.70647Licence: CC BY-NC

Cite this

Kaleck, T., Campos-Martin, R., Cano, A., Fernández, M. V., Martino-Adami, P., Kleineidam, L., Fuentes, V. M. A., Tripathi, K. P., Parveen, K., Puerta, R., de Rojas, I., Ravichandran, K. A., Peters, O., Hellmann-Regen, J., Priller, J., Gemenetzi, M., Schneider, A., Wiltfang, J., Düzel, E., ... Ramirez, A. (2025). Replication of blood DNA methylomic signatures associated with cerebrospinal fluid levels of YKL-40 and NfL biomarkers. Alzheimer's & Dementia, 21(9), Article e70647. https://doi.org/10.1002/alz.70647

@article{f280047e31374ecca4be37f3e6e8face,

title = "Replication of blood DNA methylomic signatures associated with cerebrospinal fluid levels of YKL-40 and NfL biomarkers",

keywords = "Alzheimer's disease (AD), amyloid, biomarker, blood, cerebrospinal fluid (CSF), DNA methylation, epigenetics, epigenome-wide association study (EWAS), neurofilament light (NfL), ptau, replication, YKL-40",

author = "Timo Kaleck and Rafael Campos-Martin and Amanda Cano and Fern{\'a}ndez, \{Maria Victoria\} and Pamela Martino-Adami and Luca Kleineidam and Fuentes, \{Victor M.Andrade\} and Tripathi, \{Kumar P.\} and Kayenat Parveen and Raquel Puerta and \{de Rojas\}, Itziar and Ravichandran, \{Kishore A.\} and Oliver Peters and Julian Hellmann-Regen and Josef Priller and Maria Gemenetzi and Anja Schneider and Jens Wiltfang and Emrah D{\"u}zel and Katharina Buerger and Robert Perneczky and Stefan Teipel and Christoph Laske and Frederic Brosseron and Marta Marqui{\'e} and \{van den Hove\}, \{Daniel L.A.\} and Merc{\`e} Boada and Heneka, \{Michael T.\} and Michael Wagner and Natalie Marchant and Lambert, \{Jean Charles\} and Ruth Frikke-Schmidt and Frank Jessen and Agust{\'i}n Ruiz and Alfredo Ramirez",

note = "Funding Information: The authors thank the patients and controls who participated in this project. They were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. All human subjects provided informed consent. Part of this study was funded by the German Federal Ministry of Education and Research (BMBF) within the EU program JPND (Grant number: PreADAPT project 01ED2007A and Epi-AD project 01ED1614B) and by BMBF (Grant numbers: DESCARTES project 01EK2102B and 01EK2102A). Further support was obtained from the German Research Foundation (DFG) grants numbers [RA1971/8-1] and [RA1971/7-1] to AR. N.L.M. received support for this study from the project funded by the Medical Research Council within the JPND PERSOMED (PREADAPT project grant number MR/T046171/1). The authors acknowledge the support of the Agency for Innovation and Entrepreneurship (VLAIO) grant N\textbackslash{}u00B0 PR067/21 and Janssen for the HARPONE project and the ADAPTED project the EU/EFPIA Innovative Medicines Initiative Joint Undertaking Grant N\textbackslash{}u00B0 115975. Also, the Spanish Ministry of Science and Innovation, Proyectos de Generaci\textbackslash{}u00F3n de Conocimiento grants PID2021-122473OA-I00, PID2021-123462OB-I00 and PID2019-106625RB-I00. ISCIII, Acci\textbackslash{}u00F3n Estrat\textbackslash{}u00E9gica en Salud integrated in the Spanish National R+D+I Plan and financed by ISCIII Subdirecci\textbackslash{}u00F3n General de Evaluaci\textbackslash{}u00F3n and the Fondo Europeo de Desarrollo Regional (FEDER \textbackslash{}u201CUna manera de hacer Europa\textbackslash{}u201D) grants PI17/01474, PI19/00335, PI22/01403 and PI22/00258. The support of CIBERNED (ISCIII) under the grants CB06/05/2004 and CB18/05/00010. The support from PREADAPT project, Joint Program for Neurodegenerative Diseases (JPND) grant N\textbackslash{}u00B0AC19/00097, and from DESCARTES project. The Support of Fundaci\textbackslash{}u00F3n bancaria \textbackslash{}u201CLa Caixa\textbackslash{}u201D, Fundaci\textbackslash{}u00F3n ADEY, Fundaci\textbackslash{}u00F3n Echevarne and Grifols SA (GR@ACE project). ACF received support from the Instituto de Salud Carlos III (ISCIII) under the grant Sara Borrell (CD22/00125). IdR is supported by the ISCIII 706 under the grant FI20/00215. AR is also supported by STAR Award. University of Texas System. Tx, United States, The South Texas ADRC. National Institute of Aging. National Institutes of Health. USA. (P30AG066546), the Keith M. Orme and Pat Vigeon Orme Endowed Chair in Alzheimer's and Neurodegenerative Diseases (2024\textbackslash{}u20132025) and Patricia Ruth Frederick Distinguished Chair for Precision Therapeutics in Alzheimer's and Neurodegenerative Diseases (2025\textbackslash{}u20132028). Funding Information: The authors thank the patients and controls who participated in this project. They were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. All human subjects provided informed consent. Part of this study was funded by the German Federal Ministry of Education and Research (BMBF) within the EU program JPND (Grant number: PreADAPT project 01ED2007A and Epi\textbackslash{}u2010AD project 01ED1614B) and by BMBF (Grant numbers: DESCARTES project 01EK2102B and 01EK2102A). Further support was obtained from the German Research Foundation (DFG) grants numbers [RA1971/8\textbackslash{}u20101] and [RA1971/7\textbackslash{}u20101] to AR. N.L.M. received support for this study from the project funded by the Medical Research Council within the JPND PERSOMED (PREADAPT project grant number MR/T046171/1). The authors acknowledge the support of the Agency for Innovation and Entrepreneurship (VLAIO) grant N\textbackslash{}u00B0 PR067/21 and Janssen for the HARPONE project and the ADAPTED project the EU/EFPIA Innovative Medicines Initiative Joint Undertaking Grant N\textbackslash{}u00B0 115975. Also, the Spanish Ministry of Science and Innovation, Proyectos de Generaci\textbackslash{}u00F3n de Conocimiento grants PID2021\textbackslash{}u2010122473OA\textbackslash{}u2010I00, PID2021\textbackslash{}u2010123462OB\textbackslash{}u2010I00 and PID2019\textbackslash{}u2010106625RB\textbackslash{}u2010I00. ISCIII, Acci\textbackslash{}u00F3n Estrat\textbackslash{}u00E9gica en Salud integrated in the Spanish National R+D+I Plan and financed by ISCIII Subdirecci\textbackslash{}u00F3n General de Evaluaci\textbackslash{}u00F3n and the Fondo Europeo de Desarrollo Regional (FEDER \textbackslash{}u201CUna manera de hacer Europa\textbackslash{}u201D) grants PI17/01474, PI19/00335, PI22/01403 and PI22/00258. The support of CIBERNED (ISCIII) under the grants CB06/05/2004 and CB18/05/00010. The support from PREADAPT project, Joint Program for Neurodegenerative Diseases (JPND) grant N\textbackslash{}u00B0AC19/00097, and from DESCARTES project. The Support of Fundaci\textbackslash{}u00F3n bancaria \textbackslash{}u201CLa Caixa\textbackslash{}u201D, Fundaci\textbackslash{}u00F3n ADEY, Fundaci\textbackslash{}u00F3n Echevarne and Grifols SA (GR@ACE project). ACF received support from the Instituto de Salud Carlos III (ISCIII) under the grant Sara Borrell (CD22/00125). IdR is supported by the ISCIII 706 under the grant FI20/00215. AR is also supported by STAR Award. University of Texas System. Tx, United States, The South Texas ADRC. National Institute of Aging. National Institutes of Health. USA. (P30AG066546), the Keith M. Orme and Pat Vigeon Orme Endowed Chair in Alzheimer's and Neurodegenerative Diseases (2024\textbackslash{}u20132025) and Patricia Ruth Frederick Distinguished Chair for Precision Therapeutics in Alzheimer's and Neurodegenerative Diseases (2025\textbackslash{}u20132028).",

year = "2025",

month = sep,

day = "1",

doi = "10.1002/alz.70647",

language = "English",

volume = "21",

journal = "Alzheimer's \& Dementia",

issn = "1552-5260",

publisher = "John Wiley \& Sons Inc.",

number = "9",

}

Kaleck, T, Campos-Martin, R, Cano, A, Fernández, MV, Martino-Adami, P, Kleineidam, L, Fuentes, VMA, Tripathi, KP, Parveen, K, Puerta, R, de Rojas, I, Ravichandran, KA, Peters, O, Hellmann-Regen, J, Priller, J, Gemenetzi, M, Schneider, A, Wiltfang, J, Düzel, E, Buerger, K, Perneczky, R, Teipel, S, Laske, C, Brosseron, F, Marquié, M, van den Hove, DLA, Boada, M, Heneka, MT, Wagner, M, Marchant, N, Lambert, JC, Frikke-Schmidt, R, Jessen, F, Ruiz, A & Ramirez, A 2025, 'Replication of blood DNA methylomic signatures associated with cerebrospinal fluid levels of YKL-40 and NfL biomarkers', Alzheimer's & Dementia, vol. 21, no. 9, e70647. https://doi.org/10.1002/alz.70647

TY - JOUR

T1 - Replication of blood DNA methylomic signatures associated with cerebrospinal fluid levels of YKL-40 and NfL biomarkers

AU - Kaleck, Timo

AU - Campos-Martin, Rafael

AU - Cano, Amanda

AU - Fernández, Maria Victoria

AU - Martino-Adami, Pamela

AU - Kleineidam, Luca

AU - Fuentes, Victor M.Andrade

AU - Tripathi, Kumar P.

AU - Parveen, Kayenat

AU - Puerta, Raquel

AU - de Rojas, Itziar

AU - Ravichandran, Kishore A.

AU - Peters, Oliver

AU - Hellmann-Regen, Julian

AU - Priller, Josef

AU - Gemenetzi, Maria

AU - Schneider, Anja

AU - Wiltfang, Jens

AU - Düzel, Emrah

AU - Buerger, Katharina

AU - Perneczky, Robert

AU - Teipel, Stefan

AU - Laske, Christoph

AU - Brosseron, Frederic

AU - Marquié, Marta

AU - van den Hove, Daniel L.A.

AU - Boada, Mercè

AU - Heneka, Michael T.

AU - Wagner, Michael

AU - Marchant, Natalie

AU - Lambert, Jean Charles

AU - Frikke-Schmidt, Ruth

AU - Jessen, Frank

AU - Ruiz, Agustín

AU - Ramirez, Alfredo

N1 - Funding Information: The authors thank the patients and controls who participated in this project. They were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. All human subjects provided informed consent. Part of this study was funded by the German Federal Ministry of Education and Research (BMBF) within the EU program JPND (Grant number: PreADAPT project 01ED2007A and Epi-AD project 01ED1614B) and by BMBF (Grant numbers: DESCARTES project 01EK2102B and 01EK2102A). Further support was obtained from the German Research Foundation (DFG) grants numbers [RA1971/8-1] and [RA1971/7-1] to AR. N.L.M. received support for this study from the project funded by the Medical Research Council within the JPND PERSOMED (PREADAPT project grant number MR/T046171/1). The authors acknowledge the support of the Agency for Innovation and Entrepreneurship (VLAIO) grant N\u00B0 PR067/21 and Janssen for the HARPONE project and the ADAPTED project the EU/EFPIA Innovative Medicines Initiative Joint Undertaking Grant N\u00B0 115975. Also, the Spanish Ministry of Science and Innovation, Proyectos de Generaci\u00F3n de Conocimiento grants PID2021-122473OA-I00, PID2021-123462OB-I00 and PID2019-106625RB-I00. ISCIII, Acci\u00F3n Estrat\u00E9gica en Salud integrated in the Spanish National R+D+I Plan and financed by ISCIII Subdirecci\u00F3n General de Evaluaci\u00F3n and the Fondo Europeo de Desarrollo Regional (FEDER \u201CUna manera de hacer Europa\u201D) grants PI17/01474, PI19/00335, PI22/01403 and PI22/00258. The support of CIBERNED (ISCIII) under the grants CB06/05/2004 and CB18/05/00010. The support from PREADAPT project, Joint Program for Neurodegenerative Diseases (JPND) grant N\u00B0AC19/00097, and from DESCARTES project. The Support of Fundaci\u00F3n bancaria \u201CLa Caixa\u201D, Fundaci\u00F3n ADEY, Fundaci\u00F3n Echevarne and Grifols SA (GR@ACE project). ACF received support from the Instituto de Salud Carlos III (ISCIII) under the grant Sara Borrell (CD22/00125). IdR is supported by the ISCIII 706 under the grant FI20/00215. AR is also supported by STAR Award. University of Texas System. Tx, United States, The South Texas ADRC. National Institute of Aging. National Institutes of Health. USA. (P30AG066546), the Keith M. Orme and Pat Vigeon Orme Endowed Chair in Alzheimer's and Neurodegenerative Diseases (2024\u20132025) and Patricia Ruth Frederick Distinguished Chair for Precision Therapeutics in Alzheimer's and Neurodegenerative Diseases (2025\u20132028). Funding Information: The authors thank the patients and controls who participated in this project. They were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. All human subjects provided informed consent. Part of this study was funded by the German Federal Ministry of Education and Research (BMBF) within the EU program JPND (Grant number: PreADAPT project 01ED2007A and Epi\u2010AD project 01ED1614B) and by BMBF (Grant numbers: DESCARTES project 01EK2102B and 01EK2102A). Further support was obtained from the German Research Foundation (DFG) grants numbers [RA1971/8\u20101] and [RA1971/7\u20101] to AR. N.L.M. received support for this study from the project funded by the Medical Research Council within the JPND PERSOMED (PREADAPT project grant number MR/T046171/1). The authors acknowledge the support of the Agency for Innovation and Entrepreneurship (VLAIO) grant N\u00B0 PR067/21 and Janssen for the HARPONE project and the ADAPTED project the EU/EFPIA Innovative Medicines Initiative Joint Undertaking Grant N\u00B0 115975. Also, the Spanish Ministry of Science and Innovation, Proyectos de Generaci\u00F3n de Conocimiento grants PID2021\u2010122473OA\u2010I00, PID2021\u2010123462OB\u2010I00 and PID2019\u2010106625RB\u2010I00. ISCIII, Acci\u00F3n Estrat\u00E9gica en Salud integrated in the Spanish National R+D+I Plan and financed by ISCIII Subdirecci\u00F3n General de Evaluaci\u00F3n and the Fondo Europeo de Desarrollo Regional (FEDER \u201CUna manera de hacer Europa\u201D) grants PI17/01474, PI19/00335, PI22/01403 and PI22/00258. The support of CIBERNED (ISCIII) under the grants CB06/05/2004 and CB18/05/00010. The support from PREADAPT project, Joint Program for Neurodegenerative Diseases (JPND) grant N\u00B0AC19/00097, and from DESCARTES project. The Support of Fundaci\u00F3n bancaria \u201CLa Caixa\u201D, Fundaci\u00F3n ADEY, Fundaci\u00F3n Echevarne and Grifols SA (GR@ACE project). ACF received support from the Instituto de Salud Carlos III (ISCIII) under the grant Sara Borrell (CD22/00125). IdR is supported by the ISCIII 706 under the grant FI20/00215. AR is also supported by STAR Award. University of Texas System. Tx, United States, The South Texas ADRC. National Institute of Aging. National Institutes of Health. USA. (P30AG066546), the Keith M. Orme and Pat Vigeon Orme Endowed Chair in Alzheimer's and Neurodegenerative Diseases (2024\u20132025) and Patricia Ruth Frederick Distinguished Chair for Precision Therapeutics in Alzheimer's and Neurodegenerative Diseases (2025\u20132028).

PY - 2025/9/1

Y1 - 2025/9/1

KW - Alzheimer's disease (AD)

KW - amyloid

KW - biomarker

KW - blood

KW - cerebrospinal fluid (CSF)

KW - DNA methylation

KW - epigenetics

KW - epigenome-wide association study (EWAS)

KW - neurofilament light (NfL)

KW - ptau

KW - replication

KW - YKL-40

U2 - 10.1002/alz.70647

DO - 10.1002/alz.70647

M3 - Comment/Letter to the editor

SN - 1552-5260

VL - 21

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

IS - 9

M1 - e70647

ER -