ArticlebioRxiv : the preprint server for biology2025
Mitochondrial bioenergetic signatures differentiate asymptomatic from symptomatic Alzheimer's disease.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
- Updated by
Authors and funding
5 authors.
Funding
Abstract
Asymptomatic Alzheimer's disease (AsymAD) refers to individuals who, despite exhibiting amyloid-β plaques and tau pathology comparable to Alzheimer's disease (AD), maintain cognitive performance similar to cognitively normal individuals. The resilience mechanism in these AsymAD individual remains understudied. We performed a systematic analysis comparing AsymAD and AD across multiple cohorts (ROSMAP, Banner and Mount Sinai), brain regions (BA6, BA9, BA36 and BA37) and neuronal and glial cell types using proteomics and transcriptomics data. AsymAD brains exhibited preserved mitochondrial bioenergetics, characterized by enhanced oxidative phosphorylation (OXPHOS), electron transport chain (ETC) activity, fatty acid and lipid metabolism, and branched-chain amino acid (BCAA) utilization. Pathways regulating mitochondrial complex biogenesis and calcium homeostasis were also upregulated. Key mitochondrial proteins such as MRPL47, CPT2, BCAT2, and IDH2, were consistently upregulated in AsymAD, whereas MACROD1 was downregulated. At the cellular level, excitatory neurons, including superficial, mid-layer, and deep-layer subtypes, exhibited the most preserved mitochondrial function, whereas vulnerable inhibitory subtypes, including PVALB and SST neurons, showed increased cellular abundance and bioenergetic activity. In contrast, microglia and oligodendrocytes proportions were reduced in AsymAD relative to AD. Our findings identify preserved mitochondrial bioenergetics as a defining feature of resilience in AD and suggest that enhancing NADH metabolism via NAD+ precursor-based interventions may potentially help in maintaining cognitive function despite amyloid and tau pathology.
Identifiers
What OpenQuestion holds
Registered trials
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.