Researchers identify gene expression changes linked to Alzheimer’s

A research team at Seoul National University Bundang Hospital (SNUBH) has identified gene expression patterns closely associated with the progression of Alzheimer’s disease and proposed a potential path for early diagnosis using simple blood tests.

Alzheimer’s disease is the most common cause of dementia, characterized by memory loss and cognitive decline. Because it causes irreversible brain damage as it progresses, early detection and intervention are critical. However, many patients are only diagnosed after significant disease advancement, largely due to the high burden of current diagnostic methods.

Conventional tools such as PET scans are expensive, while cerebrospinal fluid tests require invasive lumbar punctures under anesthesia, making them impractical for widespread routine screening.

To address these limitations, the research team, led by Professors Park Young-ho and Pyun Jung-min of the Department of Neurology at SNUBH, investigated whether blood-based gene expression analysis could offer a reliable alternative.

Professors Han Sang-won of the Department of Neurology at Soonchunhyang University Seoul Hospital and Nho Kwang-sik of the Department of Radiology and Imaging Sciences at Indiana Alzheimer's Disease Research Center also participated in the study.

The team collected blood samples from 523 Alzheimer’s patients enrolled at SNUBH and Seoul National University Hospital and conducted RNA sequencing to evaluate gene activity.

The study marks the first large-scale comparative analysis of gene expression between early- and late-onset Alzheimer’s patients in a Korean population.

The study revealed that patients with early-onset Alzheimer’s (before age 65) showed differential expression in 18 genes compared to healthy individuals, while those with late-onset Alzheimer’s (after age 65) showed 88 genes with altered expression patterns.

Notably, the genes SMOX and PLVAP were significantly downregulated in late-onset cases. Both genes are strongly associated with amyloid-beta protein aggregation, a hallmark of Alzheimer’s pathology.

The team also found that several genes involved in critical cellular processes -- such as energy regulation (AMPK signaling), protein degradation (ubiquitin-mediated proteolysis), and mitochondrial autophagy (mitophagy)—were dysfunctional in late-onset patients. These findings offer new biological insights into the molecular mechanisms behind Alzheimer’s progression.

The researchers emphasized the results suggested that early- and late-onset Alzheimer’s may follow distinct molecular pathways, and that gene expression profiles in blood could help differentiate between them.

The team expects that such finding could serve as a foundation for personalized treatment strategies and non-invasive diagnostic tools tailored to East Asian populations.

“This study reveals key biological pathways involved in Alzheimer’s disease through blood-based gene expression data and highlights the potential for early diagnosis and therapeutic target discovery,” Professor Park said. “We plan to conduct follow-up research with larger patient cohorts to evaluate clinical applicability.”

The findings were published in the February issue of Alzheimer’s & Dementia, the official journal of the Alzheimer’s Association.