Furthermore, it has been found using APOE ε4 mouse models that the number of hippocampal neurons containing high levels of upregulated APOE expression, increases dramatically prior to clinical diagnosis and the onset of neurodegenerative symptomology, then declines swiftly at the onset of the pathology as neurodegenerative impairment and cognitive decline become more apparent [192,193], suggesting high levels of APOE are implicated in the early onset of PD and cognitive loss but potentially less of an influence in the later stages ongoing stage of neurodegenerative and cognitive damage [192]. The gene discussed is APOE; the disease is Parkinson disease.