Ubiquitin immunochemistry as a diagnostic aid for community pathologists evaluating patients who have dementia

Alzheimer's disease is the most common cause of dementia. It is associated with genetic risk factors and at least three autosomal dominant mutations. Community pathologists are frequently asked by families to evaluate autopsy material for Alzheimer's disease. Neuropathologic diagnosis is based on te chnically difficult silver impregnation stains that may not be readily avai lable to community-based pathologists. Because immunohistochemical techniqu es are more widely accessible, we evaluated the practical utility of using a single immunohistochemical stain for diagnosing Alzheimer's disease. The ubiquitin antigen was selected because of its presence in morphologically d istinct deposits characteristic of several neurodegenerative diseases. Para ffin blocks were obtained from the Bryan Alzheimer's Disease Research Cente r Brain Bank, a repository of approximately 900 brains. Tissues from 16 ind ividuals who exhibited the entire range of Alzheimer's-type neuropathology were selected. Ubiquitin immunostains, evaluated blindly and independently by four pathologists ranging from first-year resident trainee to experience d neuropathologist, reliably stained both neuritic plaques and neurofibrill ary tangles essential for diagnosing and staging Alzheimer's disease. Nonde mented controls with early Alzheimer's-type changes were easily distinguish ed from cases of definitive Alzheimer's disease. The stains also highlighte d characteristic inclusions of Parkinson's disease or Lewy body dementia. U biquitin immunohistochemistry is a reliable, reproducible, and readily avai lable diagnostic aid for distinguishing Alzheimer's disease from other caus es of dementia.