Performance on a pattern separation task by Alzheimer’s patients shows possible links between disrupted dentate gyrus activity and apolipoprotein E ∈4 status and cerebrospinal fluid amyloid-β42 levels

摘要

IntroductionEmerging evidence suggests that decreased adult hippocampal neurogenesis represents an early critical event in the course of Alzheimer’s disease (AD). In mice, adult neurogenesis is reduced by knock-in alleles for human apolipoprotein E (ApoE) ∈4. Decreased dentate gyrus (DG) neural progenitor cells proliferation has been observed in the triple-transgenic mouse model of AD (3xTg-AD); this reduction being directly associated with the presence of amyloid-β (Aβ) plaques and an increase in the number of Aβ-containing neurons in the hippocampus. Cognitive tasks involving difficult pattern separations have been shown to reflect DG activity and thus potentially neurogenesis in both animals and man. This study involved the administration of a pattern separation paradigm to Alzheimer’s patients to investigate relationships between task performance and both ApoE status and cerebrospinal fluid (CSF) Aβ42 levels.