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Research indicates clues to early detection and prevention of Alzheimer's disease

Research indicates clues to early detection and prevention of Alzheimer's disease
Decreased expression of neuropeptides (NPs) revealed by single-cell sequencing data. (A) Cell identity shown on dimension reduction plot. (B) Cell composition of grouped replicates (two biological replicates per group). (C) Differential gene expression confirmed the identification of cell marker genes for each assigned cell type. (D) Heatmap showing expression levels of selected NP genes in each cell type in control and AD brains. (E) Gene module score for selected NPs calculated from control and AD brains visualized on dimension reduction plot. (F) Gene module score for selected GPCRs calculated from control and AD brains visualized on dimension reduction plot. (G) Total relative count of all selected NPs plotted against cell percentile ranked by decreasing cell count in selected cell types in control and AD. (H) Area under the curve (AUC) of NP transcription for selected cell types in each grouped replicate in control and AD. One-tailed Wilcoxon signed-rank test was used. (I) The AUC of GPCR transcription for selected cell types in each grouped replicate in control and AD. One-tailed Wilcoxon signed-rank test was used. *, p < 0.05; no_id, cell assigned as no id; neu, neuron; ast, astrocyte; mic, microglia; oli, oligodendrocyte; opc, oligodendrocyte progenitor cells; CPM, count per million; GPCR, G-protein-coupled receptor. Credit: Alzheimer's & Dementia (2023). DOI: 10.1002/alz.12979

Alzheimer's disease is the most common neurodegenerative disease in people over 65 and affects more than 50 million people worldwide—a number that is expected to double in 20 years. University of Minnesota scientists are examining how specific cellular activity in the brain may increase vulnerability to Alzheimer's, with findings that could offer new avenues for early detection and treatment.

In a study recently published in Alzheimer's & Dementia, College of Veterinary Medicine researchers Manci Li and Assistant Professor Peter Larsen looked at existing data from both Alzheimer's brains and healthy brains to identify the key neuropeptides—the chemical messengers that are released by —involved in Alzheimer's. They also examined the relationship between neuropeptide activity and aging.

The study found:

  • The proportion of cells releasing neuropeptides was significantly lower in Alzheimer's brains than in healthy brains.
  • Neurons with the most neuropeptide activity—those releasing higher levels and greater diversity of neuropeptides—were disproportionately absent in Alzheimer's brains.
  • Increased age coincides with decreased neuropeptide activity in the hippocampus of Alzheimer's brains, affecting an area of the brain that plays a major role in learning and memory.

"In a healthy , there are cells that can handle the demands of day-to-day life. But with Alzheimer's, these cells have either died or the connections are lost, and the cells that are left behind are struggling to keep up with the demand," said Li. "It's akin to an engine that is overworked—when the power demands are too large the engine cannot sustain the demand and beaks down."

The researchers believe this cycle of neurons overworking and breaking down contributes to the onset and progression of Alzheimer's. While further research is needed, understanding the involvement of neuropeptides in Alzheimer's offers promising avenues for by measuring neuropeptide activity. The study also suggests treatment possibilities that could prevent by simulating the effects of neuropeptides.

Upcoming research will focus on investigating neuropeptide disruption during the earliest stages of the disease, an effort that could lead to preventative treatments.

More information: Manci Li et al, Single‐cell sequencing of entorhinal cortex reveals widespread disruption of neuropeptide networks in Alzheimer's disease, Alzheimer's & Dementia (2023). DOI: 10.1002/alz.12979

Citation: Research indicates clues to early detection and prevention of Alzheimer's disease (2023, March 8) retrieved 24 April 2024 from https://medicalxpress.com/news/2023-03-clues-early-alzheimer-disease.html
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