Plasma Protein Dynamics in Alzheimer’s Disease Management

Alzheimer’s disease is hallmarked by the accumulation of amyloid β (Aβ) peptides and tau proteins, processes that are profoundly influenced by plasma protein interactions. A multitude of circulating proteins—most notably albumin, apolipoproteins and acute‐phase reactants—regulate the transport, binding and clearance of neurotoxic species. In healthy conditions, these proteins form a dynamic equilibrium with Aβ and tau, inhibiting fibrillation, promoting proteolytic degradation or facilitating receptor‐mediated uptake across the blood–brain barrier. Dysregulation of plasma protein composition, whether via altered expression, post‐translational modification or barrier permeability, can accelerate aggregate formation, neuroinflammation and synaptic dysfunction. Furthermore, quantitative changes in specific plasma proteins or glycoprotein profiles have emerged as minimally invasive biomarkers for early diagnosis, stratification of mild cognitive impairment and monitoring of disease progression. Therapeutic strategies are now exploring plasma exchange, albumin infusions and engineered carriers to restore protective protein dynamics or to sequester pathogenic peptides. A comprehensive understanding of plasma protein dynamics therefore offers a dual opportunity: refining diagnostic panels and informing novel interventions to mitigate amyloid and tau pathology.

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Plasma Protein Dynamics in Alzheimer’s Disease Management publication trend

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Technical terms

Blood–brain barrier (BBB): A selective endothelial interface that regulates exchange between circulating blood and the central nervous system.

Amyloid β (Aβ): A peptide fragment derived from amyloid precursor protein that aggregates into neurotoxic oligomers and fibrils in Alzheimer’s disease.

Liquid chromatography–tandem mass spectrometry (LC-MS/MS): An analytical technique coupling chromatographic separation with mass analysis to quantify and identify proteins in complex mixtures.

Tau phosphorylation: A post‐translational modification of the tau protein that promotes its aggregation into neurofibrillary tangles.

Microglia: Resident immune cells of the brain that mediate inflammatory responses and clearance of protein aggregates.

References

1. Amyloid β-Peptide Is Transported on Lipoproteins and Albumin in Human Plasma*. Journal of Biological Chemistry (1996).
2. Human Serum Albumin Can Regulate Amyloid-β Peptide Fiber Growth in the Brain Interstitium IMPLICATIONS FOR ALZHEIMER DISEASE*. Journal of Biological Chemistry (2012).
3. Identification of Plasma Proteins as Biomarkers for Mild Cognitive Impairment and Alzheimer’s Disease Using Liquid Chromatography–Tandem Mass Spectrometry. International Journal of Molecular Sciences (2023).
4. Mouse serum albumin induces neuronal apoptosis and tauopathies. Acta Neuropathologica Communications (2024).
5. Binding of Pro-Inflammatory Proteins S100A8 or S100A9 to Amyloid-β Peptide Suppresses Its Fibrillation. Biomolecules (2025).
6. Abnormal Serum Bilirubin/Albumin Concentrations in Dementia Patients With Aβ Deposition and the Benefit of Intravenous Albumin Infusion for Alzheimer’s Disease Treatment. Frontiers in Neuroscience (2020).