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Modulation of SPARC/Hevin Proteins in Alzheimer's Disease Brain Injury
Maximilian Strunz1, Juliet T Jarrell2, David S Cohen2
1Department of Neurology, Harvard NeuroDiscovery Center, Advanced Tissue Resource Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Abstract:
Alzheimer's disease (AD) is an age-related progressive form of dementia that features neuronal loss, intracellular tau, and extracellular amyloid-β (Aβ) protein deposition. Neurodegeneration is accompanied by neuroinflammation mainly involving microglia, the resident innate immune cell population of the brain. During AD progression, microglia shift their phenotype, and it has been suggested that they express matricellular proteins such as secreted protein acidic and rich in cysteine (SPARC) and Hevin protein, which facilitate the migration of other immune cells, such as blood-derived dendritic cells. We have detected both SPARC and Hevin in postmortem AD brain tissues and confirmed significant alterations in transcript expression using real-time qPCR. We suggest that an infiltration of myeloid-derived immune cells occurs in the areas of diseased tissue. SPARC is highly expressed in AD brain and collocates to Aβ protein deposits, thus contributing actively to cerebral inflammation and subsequent tissue repair, and Hevin may be downregulated in the diseased state. However, further research is needed to reveal the exact roles of SPARC and Hevin proteins and associated signaling pathways in AD-related neuroinflammation. Nevertheless, normalizing SPARC/Hevin protein expression such as interdicting heightened SPARC protein expression may confer a novel therapeutic opportunity for modulating AD progression.
Insights
Alzheimer's disease involves neuroinflammation, with microglia shifting phenotypes. Researchers found elevated secreted protein acidic and rich in cysteine (SPARC) and altered Hevin protein in AD brains, suggesting new therapeutic targets.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Alzheimer's disease (AD) is a progressive dementia characterized by neuronal loss and protein deposits.
- Neuroinflammation, driven by microglia, is a key feature of AD pathogenesis.
- Microglia may alter their function in AD, potentially expressing matricellular proteins.
Purpose of the Study:
- To investigate the expression and localization of SPARC and Hevin proteins in postmortem Alzheimer's disease brain tissues.
- To explore the potential role of SPARC and Hevin in AD-related neuroinflammation and immune cell infiltration.
Main Methods:
- Analysis of postmortem Alzheimer's disease brain tissues.
- Detection of SPARC and Hevin protein expression.
- Quantitative real-time PCR (qPCR) for transcript expression analysis.
Main Results:
- SPARC and Hevin proteins were detected in AD brain tissues.
- Significant alterations in SPARC and Hevin transcript expression were confirmed.
- SPARC was highly expressed in AD brain, co-localizing with amyloid-beta deposits.
Conclusions:
- SPARC and Hevin proteins are implicated in Alzheimer's disease neuroinflammation.
- Elevated SPARC expression may contribute to cerebral inflammation and tissue repair in AD.
- Modulating SPARC/Hevin expression presents a potential therapeutic strategy for Alzheimer's disease.