Dependence of cerebrospinal fluid Tau protein levels on apolipoprotein E4 allele frequency in patients with Alzheimer's disease.

Consistent pathological hallmarks of Alzheimer's disease (AD) are the formation of brain amyloid and neurofibrillary tangles (NFTs). Levels of the major protein component of NFTs, the microtubule associated protein Tau, were shown to be increased in cerebrospinal fluid (CSF) of AD patients as compared to age-matched controls. The presence of apolipoprotein E-epsilon 4 allele (APOE4) is a risk factor for sporadic and familial late-onset AD. ApoE may interact with the binding of Tau to microtubules and Tau phosphorylation in an isoform-specific manner. We investigated whether direct evidence of an isoform-specific interaction of apoE and Tau can be demonstrated in the CSF of live AD patients. We measured the apoE genotype and CSF levels of Tau in 19 patients with probable AD and 12 age-matched control subjects. We found that CSF levels of Tau increase with increasing APOE allele frequency (Spearman rank correlation, zeta = 2.71, P = 0.007). This finding may be in agreement with reports of a lesser binding of apoE4 to Tau, compared to apoE2 and apoE3, resulting in higher levels of unbound Tau in CSF.