Abstract
Glycosaminoglycans (GAGs), including heparan sulfates and chondroitin sulfates, are major components of the extracellular matrix. Upon interacting with heparin binding growth factors (HBGF), GAGs participate to the maintaintenance of tissue homeostasis and contribute to self-healing. Although several processes regulated by HBGF are altered in Alzheimer’s disease, it is unknown whether the brain GAG capacities to bind and regulate the function of HBGF or of other heparin binding proteins, as tau, are modified in this disease. Here, we show that total sulfated GAGs from hippocampus of Alzheimer’s disease have altered capacities to bind and potentiate the activities of growth factors including FGF-2, VEGF, and BDNF while their capacity to bind to tau is remarkable increased. Alterations of GAG structures and capacities to interact with and regulate the activity of heparin binding proteins might contribute to impaired tissue homeostasis in the Alzheimer’s disease brain.
Highlights
Alzheimer’s disease (AD), the major dementia disorder in the aging population, is characterized by a slow but irremediably evolving degeneration of the brain tissue
In addition to the influence of these protein aggregates in the disease development, numerous researches in the domain aim to understand how the brain extracellular matrix (ECM) can affect cells capacities to growth, survive, and assure plasticity [2]. These cellular processes are regulated from the ECM by several growth factors, most of them belonging to the family of ‘heparin binding proteins’ (HBP) and so called ‘heparin binding growth factors’ (HBGF) [3, 4]
Selective heparan sulfates (HS) and chondroitin sulfates (CS) quantification indicate that HS are the GAG species that increase in the AD hippocampus, in accord with previous studies showing HS strong accumulation in the AD brain [12, 24,25,26] and as confirmed by the stronger HS immunostaining observed in AD hippocampus cryo-sections compared to control (Fig 1b)
Summary
Alzheimer’s disease (AD), the major dementia disorder in the aging population, is characterized by a slow but irremediably evolving degeneration of the brain tissue. In addition to the influence of these protein aggregates in the disease development, numerous researches in the domain aim to understand how the brain extracellular matrix (ECM) can affect cells capacities to growth, survive, and assure plasticity [2]. Overall, these cellular processes are regulated from the ECM by several growth factors, most of them belonging to the family of ‘heparin binding proteins’ (HBP) and so called ‘heparin binding growth factors’ (HBGF) [3, 4].
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