Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study

Riley E. Kemna; Paul J. Kueck; Anneka Blankenship; Casey S. John; Chelsea N. Johnson; Zachary D. Green; Hana Mayfield; Lauren Yoksh; Lance Johnson; John P. Thyfault; Jonathan D. Mahnken; Benjamin F. Miller; Jill K. Morris

doi:10.1002/alz.70984

Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study

Riley E. Kemna
, Paul J. Kueck
, Anneka Blankenship
, Casey S. John
, Chelsea N. Johnson
, Zachary D. Green
, Hana Mayfield
, Lauren Yoksh
, Lance Johnson
, John P. Thyfault
, Jonathan D. Mahnken
, Benjamin F. Miller
, Jill K. Morris

Producción científica: Article › revisión exhaustiva

3 Citas (Scopus)

Resumen

BACKGROUND: Impaired cerebral glucose metabolism is a hallmark of Alzheimer's disease (AD). Lactate is an alternative brain fuel; however, whole-body lactate metabolism has not been measured in AD. METHODS: The Lactate for Energy and Neurocognition Trial (NCT05207397) was a single-arm trial that enrolled 24 cognitively healthy (CH) older adults and 12 cognitively impaired (CI) participants. Subjects underwent a stable isotope lactate infusion to evaluate lactate metabolism, cognitive testing, and blood biomarker analyses. pTau217, brain-derived tau (BD-tau), pTau181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total tau, and brain-derived neurotrophic factor (BDNF) were analyzed by Simoa HD-X (Quanterix). RESULTS: Lactate metabolic clearance rate did not differ between CH and CI subjects (p = 0.988). After infusion, global cognition was improved (p < 0.001) and plasma pTau217 (−33.8%, p < 0.001), BD-tau (−32.6%, p < 0.001), pTau181 (−21.4%, p < 0.001), GFAP (−39.7%, p < 0.001), and NfL (−19.5%, p < 0.001) were reduced. CONCLUSIONS: Lactate turnover was not different between diagnosis groups. Lactate infusion improved cognition and reduced AD fluid biomarkers. Highlights: Individuals with Alzheimer's disease (AD) can metabolize lactate as well as healthy controls. Lactate infusion might improve global cognition and processing speed. Lactate infusion results in significant decrease of AD fluid biomarkers.

Idioma original	English
Número de artículo	e70984
Publicación	Alzheimer's and Dementia
Volumen	21
N.º	12
DOI	https://doi.org/10.1002/alz.70984
Estado	Published - dic 2025

Nota bibliográfica

Publisher Copyright:
© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Financiación

The authors thank our participants for their willingness to give of their time for our research, as well as the KU CTSU nursing staff. This publication was supported by R01 AG062548, R01 AG081304, F30 AG076278, and F31 AG091982 through the National Institutes of Health (NIH). Further support includes R01AG081421 and R01AG080589, the CNS Metabolism COBRE (P20GM148326), and the Alzheimer's Association. This work was also supported by P30 AG072973 and the Margaret “Peg” McLaughlin and Lydia A. Walker Alzheimer's Disease Research Fund. Additional support was provided by NIH grant T32 AG078114 and the Alzheimer's Disease Research Center's Brain Health Training Program (P30 AG072973).

Financiadores	Número del financiador
National Institutes of Health (NIH)	T32 AG078114, P30 AG072973, R01AG081421, P20GM148326, R01AG080589
Alzheimer's Association	T32 AG078114, P30 AG072973

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

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10.1002/alz.70984

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Kemna, R. E., Kueck, P. J., Blankenship, A., John, C. S., Johnson, C. N., Green, Z. D., Mayfield, H., Yoksh, L., Johnson, L., Thyfault, J. P., Mahnken, J. D., Miller, B. F., & Morris, J. K. (2025). Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study. Alzheimer's and Dementia, 21(12), Artículo e70984. https://doi.org/10.1002/alz.70984

@article{b2c22e78bf8a4933b01f467f81aae89f,

title = "Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study",

abstract = "BACKGROUND: Impaired cerebral glucose metabolism is a hallmark of Alzheimer's disease (AD). Lactate is an alternative brain fuel; however, whole-body lactate metabolism has not been measured in AD. METHODS: The Lactate for Energy and Neurocognition Trial (NCT05207397) was a single-arm trial that enrolled 24 cognitively healthy (CH) older adults and 12 cognitively impaired (CI) participants. Subjects underwent a stable isotope lactate infusion to evaluate lactate metabolism, cognitive testing, and blood biomarker analyses. pTau217, brain-derived tau (BD-tau), pTau181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total tau, and brain-derived neurotrophic factor (BDNF) were analyzed by Simoa HD-X (Quanterix). RESULTS: Lactate metabolic clearance rate did not differ between CH and CI subjects (p = 0.988). After infusion, global cognition was improved (p < 0.001) and plasma pTau217 (−33.8\%, p < 0.001), BD-tau (−32.6\%, p < 0.001), pTau181 (−21.4\%, p < 0.001), GFAP (−39.7\%, p < 0.001), and NfL (−19.5\%, p < 0.001) were reduced. CONCLUSIONS: Lactate turnover was not different between diagnosis groups. Lactate infusion improved cognition and reduced AD fluid biomarkers. Highlights: Individuals with Alzheimer's disease (AD) can metabolize lactate as well as healthy controls. Lactate infusion might improve global cognition and processing speed. Lactate infusion results in significant decrease of AD fluid biomarkers.",

keywords = "Alzheimer's disease, aging, exercise, fluid biomarkers, lactate, metabolism",

author = "Kemna, \{Riley E.\} and Kueck, \{Paul J.\} and Anneka Blankenship and John, \{Casey S.\} and Johnson, \{Chelsea N.\} and Green, \{Zachary D.\} and Hana Mayfield and Lauren Yoksh and Lance Johnson and Thyfault, \{John P.\} and Mahnken, \{Jonathan D.\} and Miller, \{Benjamin F.\} and Morris, \{Jill K.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2025",

month = dec,

doi = "10.1002/alz.70984",

language = "English",

volume = "21",

number = "12",

}

TY - JOUR

T1 - Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition

T2 - The LEAN study

AU - Kemna, Riley E.

AU - Kueck, Paul J.

AU - Blankenship, Anneka

AU - John, Casey S.

AU - Johnson, Chelsea N.

AU - Green, Zachary D.

AU - Mayfield, Hana

AU - Yoksh, Lauren

AU - Johnson, Lance

AU - Thyfault, John P.

AU - Mahnken, Jonathan D.

AU - Miller, Benjamin F.

AU - Morris, Jill K.

PY - 2025/12

Y1 - 2025/12

N2 - BACKGROUND: Impaired cerebral glucose metabolism is a hallmark of Alzheimer's disease (AD). Lactate is an alternative brain fuel; however, whole-body lactate metabolism has not been measured in AD. METHODS: The Lactate for Energy and Neurocognition Trial (NCT05207397) was a single-arm trial that enrolled 24 cognitively healthy (CH) older adults and 12 cognitively impaired (CI) participants. Subjects underwent a stable isotope lactate infusion to evaluate lactate metabolism, cognitive testing, and blood biomarker analyses. pTau217, brain-derived tau (BD-tau), pTau181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total tau, and brain-derived neurotrophic factor (BDNF) were analyzed by Simoa HD-X (Quanterix). RESULTS: Lactate metabolic clearance rate did not differ between CH and CI subjects (p = 0.988). After infusion, global cognition was improved (p < 0.001) and plasma pTau217 (−33.8%, p < 0.001), BD-tau (−32.6%, p < 0.001), pTau181 (−21.4%, p < 0.001), GFAP (−39.7%, p < 0.001), and NfL (−19.5%, p < 0.001) were reduced. CONCLUSIONS: Lactate turnover was not different between diagnosis groups. Lactate infusion improved cognition and reduced AD fluid biomarkers. Highlights: Individuals with Alzheimer's disease (AD) can metabolize lactate as well as healthy controls. Lactate infusion might improve global cognition and processing speed. Lactate infusion results in significant decrease of AD fluid biomarkers.

AB - BACKGROUND: Impaired cerebral glucose metabolism is a hallmark of Alzheimer's disease (AD). Lactate is an alternative brain fuel; however, whole-body lactate metabolism has not been measured in AD. METHODS: The Lactate for Energy and Neurocognition Trial (NCT05207397) was a single-arm trial that enrolled 24 cognitively healthy (CH) older adults and 12 cognitively impaired (CI) participants. Subjects underwent a stable isotope lactate infusion to evaluate lactate metabolism, cognitive testing, and blood biomarker analyses. pTau217, brain-derived tau (BD-tau), pTau181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total tau, and brain-derived neurotrophic factor (BDNF) were analyzed by Simoa HD-X (Quanterix). RESULTS: Lactate metabolic clearance rate did not differ between CH and CI subjects (p = 0.988). After infusion, global cognition was improved (p < 0.001) and plasma pTau217 (−33.8%, p < 0.001), BD-tau (−32.6%, p < 0.001), pTau181 (−21.4%, p < 0.001), GFAP (−39.7%, p < 0.001), and NfL (−19.5%, p < 0.001) were reduced. CONCLUSIONS: Lactate turnover was not different between diagnosis groups. Lactate infusion improved cognition and reduced AD fluid biomarkers. Highlights: Individuals with Alzheimer's disease (AD) can metabolize lactate as well as healthy controls. Lactate infusion might improve global cognition and processing speed. Lactate infusion results in significant decrease of AD fluid biomarkers.

KW - Alzheimer's disease

KW - aging

KW - exercise

KW - fluid biomarkers

KW - lactate

KW - metabolism

UR - https://www.scopus.com/pages/publications/105024571097

UR - https://www.scopus.com/pages/publications/105024571097#tab=citedBy

U2 - 10.1002/alz.70984

DO - 10.1002/alz.70984

M3 - Article

C2 - 41376120

AN - SCOPUS:105024571097

SN - 1552-5260

VL - 21

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 12

M1 - e70984

ER -

Acute effects of lactate infusion on metabolism, AD biomarkers, and cognition: The LEAN study

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Financiación

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ASJC Scopus subject areas

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