Presentation made by Dr. Joanna Jankowsky at the Alzheimer Research Forum Live Webinar of March 20, 2013 - http://www.alzforum.org/res/for/journal/detail.asp?liveID=209

1. Enrichment, education, mice, and men:
Groundbreaking study raises
new questions for the field
Joanna Jankowsky, Ph.D.
Baylor College of Medicine

2. Factors that mediate risk of AD
Things we cannot control Age
Genes
Gender
Things we can modify
Environment
Education
Occupation
Exercise
Diet

3. 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

4. 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)

5. 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.