The platelet transcriptome and proteome in Alzheimer’s disease and aging: an exploratory cross-sectional study

Frontiers in Molecular Biosciences, 2023 · DOI: 10.3389/fmolb.2023.1196083 · Published: June 30, 2023

Simple Explanation

This study explores how Alzheimer's disease (AD) and aging affect platelets, which are small blood cells involved in clotting and inflammation. The researchers examined the molecular makeup of platelets from AD patients, healthy elderly people, and young individuals to understand how these conditions change platelet function. The research team analyzed platelet activation, protein content (proteome), and gene activity (transcriptome) in the three groups. They discovered that while basic platelet activation levels were similar across groups, the protein composition of platelets from AD and elderly individuals suggested higher activation compared to young individuals. Gene activity analysis indicated that AD platelets showed changes in protein breakdown processes (specifically the ubiquitin-proteasome system), while platelets from elderly individuals exhibited alterations in autophagy. These findings provide initial insights into how AD and aging might differently affect platelet function at a molecular level.

Study Duration

Not specified

Participants

39 individuals: 11 AD patients, 18 non-demented elderly, and 10 young controls

Evidence Level

Level 3; Cross-sectional study

Key Findings

1
AD and aged individuals had a proteomic signature suggestive of increased platelet activation compared with young controls.
2
Transcriptomic proﬁling suggested the dysregulation of proteolytic machinery involved in regulating platelet function, particularly the ubiquitin-proteasome system in AD and autophagy in aging.
3
Platelets in AD and aging showed dysregulation of several proteins linked to platelet activation and degranulation, including cytoskeleton and alpha-granule proteins.

Research Summary

This study investigated platelet activation, proteome, and transcriptome in Alzheimer’s disease (AD) patients, non-demented elderly, and young individuals to understand the molecular mechanisms underlying abnormal platelet function in AD and aging. The results showed similar platelet activation levels based on CD62P expression across the groups, but AD and aged individuals exhibited a proteomic signature indicative of increased platelet activation compared to young controls. Transcriptomic profiling revealed dysregulation of proteolytic machinery, with the ubiquitin-proteasome system affected in AD and autophagy in aging. These findings provide initial evidence of enhanced platelet activation in aging and offer a first glimpse into the platelet transcriptomic changes occurring in AD, suggesting potential roles for proteasomal degradation and autophagy in platelet dysfunction.

Practical Implications

Diagnostic Biomarkers

Molecular alterations in platelets might serve as diagnostic biomarkers for AD.

Therapeutic Targets

Understanding the specific molecular mechanisms underlying platelet dysfunction in AD and aging could lead to the development of targeted therapies.

Personalized Medicine

Interindividual variability in platelet function suggests the need for personalized approaches in assessing and managing thrombotic risk in AD and aging.

Study Limitations

1
Potential contamination of platelet isolates by other blood cells.
2
Lack of independent validation of identified platelet DEPs and DETs.
3
Small sample size may have limited the statistical power to detect significant differences.

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