This symposium highlights two molecules that are of increasing significance to the scientific community due to genetic evidence linking them to frontotemporal dementia and to Parkinson’s disease. Inclusions formed of these molecules have also implicated them in the pathogenesis of several other neurodegenerative conditions, including progressive supranuclear palsy, corticobasal degeneration, Pick’s disease, Lewy body disease and multiple system atrophy. The two molecules of interest are tau and synuclein, and the disorders where they have been implicated in the pathogenesis have come to be known as familial and sporadic tauopathies and synucleinopathies (15). Tau has been the focus of intense research for more than a decade after it was discovered to be a key component of neurofibrillary tangles in Alzheimer’s disease (AD)(14). That a presumably neuronal protein (3) was also a component of glial lesions in a host of non-Alzheimer degenerative diseases (7) was unexpected and offered an entirely new perspective on neurodegenerative disorders. This group of disorders, with not only neuronal, but also oligodendroglial and astrocytic filamentous tau inclusions, has come to be known as the tauopathies (15, 30)(Figure 1). In this symposium Komori describes the range of tau-positive glial lesions, and he discusses the current state of knowledge about their differential diagnostic significance in diagnostic neuropathology (23). The recent discovery of mutations in the tau gene (17), which is located on chromosome 17 (1), and their relationship to frontotemporal dementias with parkinsonism (FTDP-17) has lead to renewed interest in tau. This new knowledge has also opened exciting opportunities to study the role of the mutations on normal functions of tau and how they are perturbed in the tauopathies. The biochemical profile of tau in the familial and sporadic tauopathies is discussed by Buée and Delacourte (4), while Yen and co-workers describe the effects FTDP-17 mutations have on the normal functional properties of tau and the tendency of tau to form filamentous structures (35). Finally, Trojanowski and Lee discuss FTDP-17 mutations in the context of approaches to model tauopathies in transgenic mice (31).

Synuclein was initially discovered as a component of the other major histopathologic lesion of AD, the senile plaque (19). A fragment of synuclein that co-purified with amyloid was termed non-amyloid component of plaques. In this symposium Hashimoto and Masliah review the biology of α-synuclein and its family of related molecules, including β-synuclein and γ-synuclein (16). They focus on the possible roles that it may have in amyloidosis and as a seed for intracellular fibril formation in Lewy body disease. Interest in synuclein was fueled by the discovery that its gene, which is located on chromosome 4 (6), was mutated in rare familial forms of Parkinson’s disease (27). Furthermore, α-synuclein was subsequently shown to be present in Lewy bodies and Lewy-related neuritic pathology in Parkinson’s disease (29). An update on the genetics of Parkinson’s disease is also found in the Hashimoto and Masliah review (16). More recently synuclein has also been shown to be present in neuronal and glial inclusions not only in Lewy body disease, but also in multiple system atrophy (MSA)(2)(Figure 2). Given the fundamental nature of these α-synuclein containing lesions to these disorders, MSA and Lewy body disease have been considered to be synucleinopathies. In this symposium Dickson and co-workers discuss MSA and biochemical alterations in α-synuclein in this disorder (11) and the concept of synucleinopathy.