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 AD

Things we cannot control AgeGenesGender

Things we can modify EnvironmentEducationOccupationExerciseDiet

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

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 effectthat must be taken into account when assessing patients

and conducting epidemiological studies

No formal education1-6 years of educationMiddle school or higher

• Method: NTG, APP, PS1, and APP/PS1 mice reared in EE or SH from 2-9mo

• Outcome: Behavioral improvement in MWM, reversal testing,

and RAWM by ALL genotypes in EE

despite paradoxical increase in Ab and amyloid

Our early efforts to model education in APP mice

Jankowsky et al., J Neurosci (2005)

• Current work by Li et al.raises possibility that effectwas due to enhancementof b2-AR signaling

• 2006 study by Ni et al.shows that b2-AR increasesg-secretase activity and Ab

• Does b2-AR both acceleratedisease yet protect againstthe consequences?

Important questions raised by the current study

• What is the mechanism of protection against oAb? Does oAb bindb2-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 oAbexceed lifespan if started later in life?

• What does this mean for the millions of Americans now treated withb-blockers for high blood pressure?

Are we causing one disease by curing another?

Congratulations to Shaomin Li and colleagues for an important contributionto discourse in the field.