Werner syndrome (WS) is an autosomal recessive disorder associated with evidence of accelerated systemic aging, but generally thought not to involve the central nervous system. We examined two WS cases utilizing a sensitive Bielschowsky silver stain and immunohistochemistry for amyloid beta peptide (A beta) and hyperphosphorylated tau. Extensive frontal and temporal lobe A beta deposition was observed in the oldest (age 57 years) WS case and restricted neurofibrillary pathology was seen in the medial temporal lobe of both cases. The severity of A beta deposition in the medial temporal lobe of the oldest case exceeded that observed in our control cases and that reported in the literature. Our findings suggest that the apparent accelerated aging observed in WS can involve the central nervous system and may implicate the recently observed WRN locus mutation associated with WS in the neuropathology of aging and aging-associated diseases.