Enrichment, education, mice, and men:Groundbreaking study raisesnew questions for the field Joanna Jankowsky, Ph.D. Baylor College of Medicine
Factors that mediate risk of ADThings we cannot control Age Genes GenderThings we can modify Environment Education Occupation Exercise Diet
A historical perspective on education and AD• 1988: James Mortimer predicted cognitive activity would influence risk of AD• 1990: Shanghai study confirmed his prediction Method: Volunteers grouped by education No formal education 1-6 years of education Middle school or higher Outcome: Prevalence of AD after age 75 2x higher in non-educated than in those with schooling• Since then, replicated in cohorts around the world as a cross-cultural, cross-racial effect that must be taken into account when assessing patients and conducting epidemiological studies
Our early efforts to model education in APP mice• Method: NTG, APP, PS1, and APP/PS1 mice reared in EE or SH from 2-9 mo• Outcome: Behavioral improvement in MWM, reversal testing, and RAWM by ALL genotypes in EE despite paradoxical increase in Ab and amyloid• Current work by Li et al. raises possibility that effect was due to enhancement of b2-AR signaling• 2006 study by Ni et al. shows that b2-AR increases g-secretase activity and Ab• Does b2-AR both accelerate disease yet protect against the consequences? Jankowsky et al., J Neurosci (2005)
Important questions raised by the current study• What is the mechanism of protection against oAb? Does oAb bind b2-AR directly, or do their effects intersect farther downstream?• Will b2-AR activation be as effective against chronic oAb exposure?• How long does the protection last after mice are removed from EE? (and how does this relate to timing of education/occupation in humans?)• Will the duration of enrichment needed for protection against oAb exceed lifespan if started later in life?• What does this mean for the millions of Americans now treated with b-blockers for high blood pressure? Are we causing one disease by curing another?Congratulations to Shaomin Li and colleagues for an important contribution to discourse in the field.