Archived

This content is available here for research, reference, and/or recordkeeping.

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.

Document Type

Article

Publication Date

12-1-2025

Notes/Citation Information

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

Digital Object Identifier (DOI)

10.1002/alz.70984

Archival?

Archival

Download

Share

COinS