Combining the knowledge of forebrain organoids and the ECM development in AD pathology, our studies used heparin (competes for Aβ affinity with HSPG), heparinase III (digests HSPGs), chondroitinase (digests CSPGs), and hyaluronic acid (HA) to treat the cortical and hippocampal forebrain spheroids/organoids exposed to Aβ42 oligomers [166]. Here, HSPG2 is linked to Alzheimer disease.