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Researchers are interested in learning how different Alzheimer's biomarkers interact with each other and with genetic factors to predict disease progression. In one study, Alzheimer's Disease Neuroimaging Initiative (ADNI) investigators studied interactions among CSF beta-amyloid levels, gene risk factors (in particular, the APOE e4 gene), and hippocampal volume loss (Chiang et al., 2011). The study involved nearly 300 older volunteers with normal cognition, MCI, or Alzheimer's.

For all groups, participants who had lower (i.e., abnormal) beta-amyloid levels in CSF at the start of the study showed greater loss of hippocampal volume over a 1-year period. In the MCI group, APOE e4 carriers showed greater hippocampal volume loss than non-carriers, and individuals with both the APOE e4 allele and low beta-amyloid showed greater hippocampal volume loss than would be expected from either risk factor alone. These results suggest abnormal beta-amyloid processing may accelerate degenerative brain changes associated with the APOE e4 allele.

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