ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026
Mitochondrial NADK2-dependent NADPH controls tau oligomer uptake in human neurons.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Metabolism and oxygen tension in Alzheimer's disease mouse model using two-photon FLIM-PLIM microscopy.Neurophotonics · 2026Article
- Tau oligomers modulate synapse fate by eliciting progressive bipartite synapse dysregulation and synapse loss.Molecular neurodegeneration · 2026Article
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11 authors.
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Abstract
introductionReduced brain energy metabolism, mitochondria dysfunction, and extracellular tau oligomer buildup characterize Alzheimer's disease (AD), but how these phenomena cooperatively promote neurodegeneration is poorly understood. We now report that tau oligomers (TauOs) pathologically coordinate mitochondrial metabolism with increased expression of a plasma membrane (PM) tau receptor.
methodsMitochondrial energy metabolism was recorded using two-photon fluorescence lifetime microscopy of mitochondrial nicotinamide adenine dinucleotide phosphate (NADPH) in live human neurons and PS19 mouse brain.
resultsRecombinant or human brain-derived TauOs upregulate expression of the mitochondrial NAD+ kinase, mitochondrial NAD kinase 2 (NADK2), and by extension, de novo NADPH synthesis. This process controls expression of low-density lipoprotein receptor-related protein 1 (LRP1), a major PM receptor for tau, thereby establishing a vicious cycle for further TauO internalization. Upregulation of the NADK2-NADPH pathway was detected in live presymptomatic PS19 mouse brains and in AD patient-derived neurons. DISCUSSION: Upregulation of mitochondrial NADK2-dependent NADPH controls a key step in TauO toxicity and may represent an early stage in human AD.
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