Post mortem sampling of the brain and other tissues in neurodegenerative disease


S Love, Department of Neuropathology, Institute of Clinical Neuroscience, Frenchay Hospital, Bristol BS16 1LE, UK. e-mail:


The importance of the autopsy in neurodegenerative disease is often not appreciated. Yet clinical diagnosis of neurodegenerative disease is relatively inaccurate, many neurodegenerative diseases are inherited or are associated with specific genetic risk factors, and several non-transmissible neurodegenerative diseases may be confused clinically with prion diseases. In all these cases, the autopsy is the only practical way in which brain tissue can be obtained for diagnosis. The pathologist should ensure that consent by the next-of-kin to post mortem examination is based on clear information as to the nature, scope and limitations of the autopsy, and that any constraints on retaining brain and other tissues are documented. The autopsy should be preceded by a careful review of the clinical notes and ante mortem studies, and consideration of the possible and likely pathological processes. This may suggest the need to retain fixed or frozen samples of cerebrospinal fluid, skeletal muscle, peripheral nerve and other tissues in addition to brain and spinal cord. Ideally, the brain should be fixed intact for 2–3 weeks before it is sliced and blocks are taken. If the period of fixation is limited to a few days only, it is best to slice the brain whilst it is fresh and to allow the diagnostically relevant slices to fix flat; after about 3 days the fixed slices can be sliced further, examined macroscopically and sampled. Even if consent is limited to the retention of only a few tissue samples for histology, a reasonably confident diagnosis can still usually be made, provided that the sampling is careful and systematic. The selection of blocks or brain and spinal cord for histology should be based on internationally accepted guidelines for the pathological diagnosis of different types of neurodegenerative disease, where such guidelines are available. Illustrations are provided to indicate which regions of the brain are critical to establishing a diagnosis in the main categories of neurodegenerative disease. When difficulties arise in the pathological diagnosis of neurodegenerative disease, inadequate post mortem sampling or rapid processing of poorly fixed brain tissue is usually to blame.