Figure 1
Figure 1From Alzheimer's Research & Therapy · CC BY-NC-ND
Brain agingHumans

Aspirin initiation before 65 links to lower Alzheimer's risk

Across electronic health records and insurance claims databases, starting aspirin before age 65 was consistently associated with lower incident Alzheimer’s disease risk.

Alzheimer's Research & Therapy

In human health records and cortical organoids, researchers evaluated aspirin as a repurposed candidate against Alzheimer’s disease. The authors generated disease expression signatures from genetically predicted transcriptomic changes in bulk tissues and microglia. They then queried Connectivity Map profiles to pinpoint compounds predicted to reverse those signatures, identifying aspirin across multiple models. The team tracked clinical outcomes in longitudinal electronic health records from Vanderbilt University Medical Center and the NIH All of Us Research Program, alongside national claims data. Across these datasets, starting aspirin before age 65 was consistently associated with reduced risk of incident Alzheimer’s disease. Cumulative drug exposure and APOE ε4 carrier status also appeared to influence the association. In lab tests, aspirin opposed Alzheimer’s-related neuronal pathway changes more effectively in wild-type cortical organoids than in an Alzheimer’s disease organoid model.

Why it matters

Repurposing existing drugs by pairing genetic and transcriptomic signatures with clinical records offers a path to identify accessible therapies for age-related neurodegenerative decline.

Caveats

The clinical findings come from observational databases that cannot establish causation. Additionally, cellular experiments showed that aspirin exerted weaker transcriptomic effects in an organoid model of Alzheimer’s than in wild-type cells.

The paper

Integrating genetically predicted transcriptomic signatures with longitudinal real-world data for drug repurposing in Alzheimer’s disease

Grabowska ME, Chen R, Zhou Y et al.

Alzheimer's Research & Therapy · 2 Oct 2026

doi.org/10.1186/s13195-026-02215-0

More on Brain aging

See all
bioRxivHumansPreprint

Human neurons accumulate far more mutations over lifespan than shorter-lived mammals

Cortical neurons gain mutations at similar yearly rates across six species, leaving aged humans with uniquely high mutational burdens and…Cortical neurons gain mutations at similar yearly rates across six species, leaving aged humans with uniquely high mutational burdens and transcriptomic dysregulation. In a preprint analyzing humans, chimpanzees, rhesus macaques, marmosets, ferrets, and mice, researchers evaluated genomic…

Distinct cerebral cortical neuronal subtypes display subtle yet specific differences in their mutational landscape.
bioRxivAnimalsPreprint

CAR T cells targeting inflammatory bone marrow progenitors restore cognition in aged mice

Clearing these peripheral myeloid cells remodeled brain macrophages and improved cognitive performance without requiring the engineered immune cells…Clearing these peripheral myeloid cells remodeled brain macrophages and improved cognitive performance without requiring the engineered immune cells to enter the brain. In aged mice and mouse models of Alzheimer's disease, researchers tested CAR T cell therapies targeting inflammatory…

bioRxivAnimalsPreprint

Extracellular cGAMP drives neuroinflammation and premature aging phenotypes in mice

Loss of the cGAMP-degrading enzyme ENPP1 allows microglia-derived signaling molecules to trigger STING-dependent inflammation across multiple brain…Loss of the cGAMP-degrading enzyme ENPP1 allows microglia-derived signaling molecules to trigger STING-dependent inflammation across multiple brain cell types. In a mouse study, researchers found that advanced age and experimental autoimmune encephalomyelitis cause microglia to accumulate…

bioRxivCellsPreprint

Directly converted human neuronal spheroids preserve donor age and model Alzheimer disease

The three-dimensional cell platform maintains biological aging markers while spontaneously developing hallmark pathologies of sporadic Alzheimer…The three-dimensional cell platform maintains biological aging markers while spontaneously developing hallmark pathologies of sporadic Alzheimer disease. In a new preprint, researchers developed directly induced neuronal spheroids using primary fibroblasts from young, unimpaired aged, and…

medRxivHumansPreprint

Auditory nerve myelin degeneration defines a subtype of age-related hearing loss

Researchers linked poor auditory nerve synchrony and myelin degradation to amplified communication difficulties in older humans, beyond standard…Researchers linked poor auditory nerve synchrony and myelin degradation to amplified communication difficulties in older humans, beyond standard hearing thresholds. In a human study detailed in a preprint, researchers investigated how auditory nerve changes affect hearing in older adults.

Aging modifies the association between auditory nerve response amplitude and neural synchrony.