Heparan Sulfate and Chondroitin Sulfate Proteoglycans as Detectable Biomarkers in Alzheimer's Disease

Abstract

With the focus of researchers and physicians shifting from treating patients at late stages of neurodegeneration to creating longitudinal brain health records for early diagnosis, viable biomarkers for Alzheimer’s disease will be needed. Most detectable symptoms of neurodegenerative disorders leave a wide range of potential diagnoses that cannot be narrowed down without brain biopsies or analysis at autopsy. Heparan sulfate and chondroitin sulfate proteoglycans are the most important classes of extracellular matrix molecules in the brain and their prevalence in several important neural structures implicates them in the formative mechanisms of the characteristic plaques and tangles in the Alzheimer’s brain. Heparan sulfate and chondroitin sulfate proteoglycans undergo changes and trigger modifications of nearby extracellular molecules during Alzheimer’s pathogenesis. The disruption of the amyloid balance in the brain in Alzheimer’s is the basis of the most accurate biomarkers currently used for Alzheimer’s diagnosis and care, but proteoglycan dysfunction is molecularly and temporally upstream of amyloid aggregation. Picking out the most representative brain trends in Alzheimer’s from the structural variance and downstream effects of heparan sulfate and chondroitin sulfate proteoglycan families could show signs of pathogenesis in patients earlier than any other measure. Biomarkers that measure sulfation patterns of proteoglycans in the cerebrospinal fluid may help individual patients to contextualize cognitive and behavioral symptoms or prevent them before they even emerge.