Clinico-pathological correlations in neurodegeneration

Abstract

During the last years, Acta Neuropathologica has published a number of cluster fascicles focused on special neuropathological subjects, e.g., Alzheimer, Lewy body and prion diseases, brain tumor diagnosis, and animal models of nervous system diseases. Knowledge about clinicopathological correlations in neurodegenerative disorders has been widened, but also obscured by the rapid progress of clinical and basic sciences in detecting essential molecular and genetic backgrounds of these devastating disorders, leading to considerable changes in their traditional classifications and demonstrating multiple, often clinically similar, but biologically different subgroups. The classification of neurodegenerative diseases, previously based on the anatomical systems involved, has progressively been replaced by biologically and genetically defined groups, both promoting and obscuring the clinicians’ views and making exact clinical diagnoses occasionally difficult without molecular pathological background. Neuropathologists as clinical neuroscientists are at the forefront of correlating histological and molecular changes in the brain with neurological features. Accordingly, the idea of reviewing the clinico-pathological correlations of the major neurodegenerative diseases, which should be of interest to both clinicians and basic neuroscientists, was born at the XVIIth International Congress of Neuropathology in Salzburg, Austria, in September 2010. Manuel F. Casanova and colleagues present a critical review of the neuroimaging and morphological correlates of behavioral and psychological symptoms in dementia (BPSD), a subject hitherto rarely discussed in this global form. The review of the literature indicates that BPSD are the expression of regional rather than diffuse brain pathology: psychotic symptoms in demented patients are preferentially associated with the involvement of frontal and/or limbic regions, visual hallucinations with damage to the occipital lobes, apathy with the anterior cingulate gyrus, while white matter lesions appear to be significant for depression. However, BPSD may not be explained by neuropathological findings alone, but are influenced by genetic, neurochemical, environmental, personality, social, and other factors that need further elucidation. Keith A. Josephs and coworkers, based on the pooled data from a number of large clinico-pathological studies, review the neuropathological background of phenotypical variability in frontotemporal dementias (FTD) that currently are classified into three main groups based on the major protein deposits in the brain; frontotemporal lobar degeneration (FTLD)-tau, -TDP, and -FUS. These groups and their specific pathology underly a number of clinical syndromes and the relationships of which are critically discussed. Although strong relationships were identified between FTD with motor neuron disease and FTLD-TDP; semantic dementia and FTLD-TDP, FTLD-tau, and progressive supranuclear palsy (PSP); and the corticobasal syndrome with FTLD-tau, other clinico-pathological relationships are still not clear, although there are some associations between clinical phenotypes and FTLD pathologies. While there remain diagnostic challenges, clinical diagnosis may often predict molecular pathology. Richard Reynolds’ group, based on the broad experience of the UKMS Tissue Bank, present a profound and critical K. A. Jellinger (&) Institute of Clinical Neurobiology, Kenyongasse 18, 1070 Vienna, Austria e-mail: kurt.jellinger@univie.ac.at