Tapping into the biology of Alzheimer disease

In this issue of Neurology®, a research team from the Alzheimer's Disease Center at Washington University St. Louis show how the symptomatic course and CSF biomarkers of Alzheimer disease (AD) are influenced by age, education, and brain volume. Roe et al.¹ replicate observations of others that the CSF levels of amyloid-β peptide (Aβ₄₂), tau, and phospho-tau₁₈₁ predict future risk for the development of dementia.² They then go on to demonstrate that education and normalized whole brain volume (nWBV) modify the predictive value of the CSF biomarkers for future dementia. The terms “cognitive reserve” and “brain reserve” are used in this context to signify level of educational attainment or brain size, representing an underlying theoretical construct, that of resilience of cognitive functioning in the face of brain pathology. Although the predictive accuracy of the CSF biomarkers with or without the added variables was still modest over the relatively short period of observation, the results of Roe et al. highlight some of the principles that govern the evolution of dementia due to AD.

A recently developed perspective on AD^3,4 has sought …