Cerebrospinal fluid β-amyloid _1-42 and tau in control subjects at risk for Alzheimer's disease: The effect of APOE ε4 allele

Cerebrospinal fluid (CSF) measures of β-amyloid _1-42 and tau are linked with the known neuropathology of Alzheimer's disease (AD). Numerous lines of evidence have also suggested that individuals with at least one APOE ε4 allele on chromosome 19 are at increased risk of developing AD. We tested these CSF markers in groups of subjects with AD and healthy older control subjects, using the absence or presence of the APOE ε4 allele as a predictive variable in the search for possible prognostic biomarkers of AD. We assessed the levels of β-amyloid _1-42 and total tau in the CSF of 292 subjects (142 control subjects and 150 subjects with mild-to-moderate AD), who were research participants at the National Institute of Mental Health. The group of control subjects was enriched with a high percentage of subjects with a positive family history of AD. All subjects underwent extensive global cognitive testing. When divided according to the absence or presence of the APOE ε4 allele, the control subjects with at least one ε4 allele had significantly lower CSF β-amyloid _1-42 but not tau levels than control subjects without an APOE ε4 allele (p < 01). As expected, the AD patients had lower levels of CSF β-amyloid _1-42 and higher CSF tau levels than the normal control group (p <. 01). The association of APOE ε4 allele and lower, more AD-like levels of CSF β-amyloid _1-42 in older control subjects is consistent with previous studies showing possible neuroimaging and cognitive abnormalities with ε4 carriers and suggests that CSF β-amyloid _1-42 decreases might represent an early biomarker of AD. Longitudinal follow-up is of course required to verify whether this biomarker is indeed predictive of clinical conversion to AD.