Objective To see if the distribution patterns of phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) intraneuronal inclusions in amyotrophic lateral sclerosis (ALS) permit recognition of neuropathological stages. Methods pTDP-43 immunohistochemistry was performed on 70 μm sections from ALS autopsy cases (N=76) classified by clinical phenotype and genetic background. Results ALS cases with the lowest burden of pTDP-43 pathology were characterized by lesions in the agranular motor cortex, brainstem motor nuclei of cranial nerves XII-X, VII, V, and spinal cord α-motoneurons (stage 1). Increasing burdens of pathology showed involvement of the prefrontal neocortex (middle frontal gyrus), brainstem reticular formation, precerebellar nuclei, and the red nucleus (stage 2). In stage 3, pTDP-43 pathology involved the prefrontal (gyrus rectus and orbital gyri) and then postcentral neocortex and striatum. Cases with the greatest burden of pTDP-43 lesions showed pTDP-43 inclusions in anteromedial portions of the temporal lobe, including the hippocampus (stage 4). At all stages, these lesions were accompanied by pTDP-43 oligodendroglial aggregates. Ten cases with C9orf72 repeat expansion displayed the same sequential spreading pattern as non-expansion cases but a greater regional burden of lesions, indicating a more fulminant dissemination of pTDP-43 pathology. Interpretation pTDP-43 pathology in ALS possibly disseminates in a sequential pattern that permits recognition of four neuropathological stages consistent with the hypothesis that pTDP-43 pathology is propagated along axonal pathways. Moreover, the fact that pTDP-43 pathology develops in the prefrontal cortex as part of an ongoing disease process could account for the development of executive cognitive deficits in ALS.

Neurodegenerative diseases (NDs) are defined by the accumulation of abnormal protein deposits in the central nervous system (CNS), and only neuropathological examination enables a definitive diagnosis. Brain banks and their associated scientific programs have shaped the actual knowledge of NDs, identifying and characterizing the CNS deposits that define new diseases, formulating staging schemes, and establishing correlations between neuropathological changes and clinical features. However, brain banks have evolved to accommodate the banking of biofluids as well as DNA and RNA samples. Moreover, the value of biobanks is greatly enhanced if they link all the multidimensional clinical and laboratory information of each case, which is accomplished, optimally, using systematic and standardized operating procedures, and in the framework of multidisciplinary teams with the support of a flexible and user-friendly database system that facilitates the sharing of information of all the teams in the network. We describe a biobanking system that is a platform for discovery research at the Center for Neurodegenerative Disease Research at the University of Pennsylvania.

Political consumerism has recently generated academic interest among political participation researchers. While some scholars underscore political consumerism as an emerging civic and political engagement, others discredit its democratic potentials. Drawing on two national survey samples in 2002 that measured both boycotting and ‘buycotting’, this study examines political consumers' demographic backgrounds, socio‐political attitudes, issue orientations and their status of civic and political participation. Findings suggest that: (1) boycotters and buycotters should be distinguished because their demographic backgrounds are substantially different; (2) political consumers possess post‐material values and are mainly interested in lifestyle‐oriented social issues; and (3) political consumers are more active political participants. Theoretical implications of the findings and an agenda for future studies are also discussed.

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