The catastrophic loss of cerebral neurons in Alzheimer's disease (AD) is not fully understood. Since serum proteins are known to extravasate into the brain parenchyma in AD due to blood-brain barrier (BBB) dysfunction, this study was designed to explore the possibility that neuronal cell death may be the consequence of the anomalous presence of serum proteins in the brain. As compared to age-matched, non-demented 'control' brain tissues, highly significant increases of immunoglobulins (Igs) were detected in parenchyma, which were associated with vessels in the AD brain tissues. Also, there were dramatic increases of +Ig-neurons in areas with greater parenchymal Ig reactivity. The Ig labeling extended throughout the cell, which showed neurodegenerative apoptotic features that were not observed in -Ig-neurons. Thus, the presence of +Ig-neurons in AD brains implies a critical link between the faulty BBB and neuronal death through an autoimmune mechanism.