To investigate how PNN deficits impact AD pathology, we generated 5xFAD+/−/Acanfl/fl/Nestin-Cre+/− by crossing 5xFAD mice to floxed Acan and Nestin-Cre mice,49 which results in loss of Acan in neural lineage cells. The gene discussed is NES; the disease is Alzheimer disease.