CSF tau/Aβ42 ratio for increased risk of mild cognitive impairment -: A follow-up study

Background: Processes of Alzheimer disease (AD) likely begin years prior to the onset of cognitive impairment (latent AD), progress though a prodromal phase of mild cognitive impairment (MCI), and culminate in dementia. While many studies have evaluated CSF tau and A beta(42) as biomarkers of the dementia or prodromal stages of AD, we are unaware of any study to evaluate these potential CSF biomarkers of latent AD. Methods: We determined the ratio of CSF tau/A beta(42) (T/A beta) using Luminex reagents in 129 control individuals that spanned from 21 to 100 years of age; for comparison we included patients with MCI (n = 12), probable AD (n = 21), or other neurodegenerative diseases (n = 12). Results: We identified 16% of the control group with abnormally elevated CSF T/A beta; all were 53 years or older. Using age-matched controls with normal CSF T/A beta we showed that the high CSF T/A beta subgroup of controls had significantly increased frequency of the epsilon 4 allele of the apolipoprotein E gene and significantly increased risk of conversion to MCI during follow-up of up to 42 months suggesting that they had latent AD at the time of lumbar puncture. Conclusions: These generally applicable methods establish cutoff values to identify control individuals at increased risk of conversion to mild cognitive impairment which may be useful to people weighing the risk-benefit ratio of new preventive therapeutics and to researchers striving to enrich clinical trial populations with people with latent Alzheimer disease.