Previously it was reported that Alzheimer's disease (AD) patients have reduced 
amyloid (Aβ 1-42) and elevated total tau (t-tau) and phosphorylated tau (p-tau 
181p) in the cerebro-spinal fluid (CSF), suggesting that these same measures 
could be used to detect early AD pathology in healthy elderly (CN) and mild 
cognitive impairment (MCI). In this study, we tested the hypothesis that there 
would be an association among rates of regional brain atrophy, the CSF 
biomarkers Aβ 1-42, t-tau, and p-tau 181p and ApoE ε4 status, and that the 
pattern of this association would be diagnosis specific. Our findings primarily 
showed that lower CSF Aβ 1-42 and higher tau concentrations were associated with 
increased rates of regional brain tissue loss and the patterns varied across the 
clinical groups. Taken together, these findings demonstrate that CSF biomarker 
concentrations are associated with the characteristic patterns of structural 
brain changes in CN and MCI that resemble to a large extent the pathology seen 
in AD. Therefore, the finding of faster progression of brain atrophy in the 
presence of lower Aβ 1-42 levels and higher p-tau levels supports the hypothesis 
that CSF Aβ 1-42 and tau are measures of early AD pathology. Moreover, the 
relationship among CSF biomarkers, ApoE ε4 status, and brain atrophy rates are 
regionally varying, supporting the view that the genetic predisposition of the 
brain to amyloid and tau mediated pathology is regional and disease stage 
specific.