Despite the fact that multiple sclerosis (MS) and Alzheimer's disease (AD) share common neuroimmunological features, interferon beta 1a (IFNβ1a), the well-established treatment for the prevention of disease progression and cognitive decline in MS patients, has never been used in AD. We evaluated the safety and efficacy of IFNβ1a in subjects affected by mild-to-moderate AD in a double-blind, randomized, placebo-controlled, multicenter pilot study. Forty-two early Alzheimer's patients were randomized to receive either a 22 mcg subcutaneous injection of IFNβ1a or placebo three times per week. A treatment period of 28 weeks was followed by 24 weeks of observation. IFNβ1a was well tolerated and adverse events were infrequent and mild to moderate. Although not statistically significant, a reduction in disease progression during follow-up was measured in IFNβ1a-treated patients by the Alzheimer's Disease Assessment Scale cognitive subscale. Interestingly, the treatment group showed significant improvements in the Instrumental Activities of Daily Living and Physical Self-maintenance Scale. This study suggests that IFNβ1a is safe and well tolerated in early AD patients, and its possible beneficial role should be further investigated in larger studies.