Ventricular enlargement is a common finding among patients with Alzheimer's disease (AD), and has recently been shown to occur from an early disease stage. A possible pathophysiological link between ventricular enlargement and AD has been suggested, with faulty cerebrospinal fluid (CSF) clearance implicated as one possible mechanism. We examined whether ventricular enlargement is associated with CSF amyloid beta (Aβ) early in the disease, even before cognitive symptoms are present, as one would expect to observe this relationship if CSF clearance is impaired. Baseline CSF biomarker data (Aβ, tau, and phosphorylated tau) and MRI brain volumetric measures were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Data from 288 participants classified as cognitively asymptomatic (n = 87), mild cognitive impairment (MCI; n = 136), or mild AD (n = 65) were analyzed by multiple linear regression with brain volumes and age as independent variables, and each biomarker as dependent variables. Ventricular volume was negatively associated with CSF Aβ in APOE ε4-positive cognitively asymptomatic participants. In contrast, ventricular volume was not associated with Aβ among ε4-positive MCI or AD patients. Tau concentrations were negatively associated with ventricular volume among ε4-positive AD patients. These findings indicate that increased ventricular volume is associated with decreased CSF Aβ among cognitively asymptomatic people who are at risk for AD based on ε4 genotype. The effects of APOE ε4 genotype on these relationships are currently not well understood, but may involve impaired CSF clearance and possibly CSF-blood-brain barrier dysfunction.