Chapter

Alterations in tau metabolism in amyotrophic lateral sclerosis with cognitive impairment

Michael J. Strong, Wencheng Yang, May Gohar and Wendy L. Strong

in Amyotrophic Lateral Sclerosis and the Frontotemporal Dementias

Published on behalf of Oxford University Press

Published in print October 2012 | ISBN: 9780199590674
Published online November 2012 | e-ISBN: 9780191753466 | DOI: http://dx.doi.org/10.1093/med/9780199590674.003.0023
Alterations in tau metabolism in amyotrophic lateral sclerosis with cognitive impairment

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As described throughout this text, the concept that amyotrophic lateral sclerosis (ALS) is a disorder solely of the motor system has been replaced by the understanding that it is often associated with one or more syndromes of frontotemporal dysfunction. Although these clinical manifestations can be attributed to a frontotemporal lobar degeneration (FTLD), not dissimilar in its features from that observed in a wide range of other frontotemporal dementias (FTD) (Figure 23.1), until recently the biological basis of the FTLD associated with ALS was unknown. To a large extent, this changed with the discovery that the transactive response DNA-binding protein of 43 kDa (TDP-43) is the core constituent of the ubiquitinated intraneuronal aggregates observed in the FTLDs with ubiquitin prominent pathology (FTLD-U), and that this property is shared with the ubiquitinated aggregates of ALS. As discussed by Cairns (Chapter 18), this has led to the current concept that ALS is best classified among the FTLDs in which TDP-43 deposition is the prominent pathology (FTLD/TDP). The implication here is that the fundamental biological basis for the frontotemporal syndromes of ALS is thus a pathological transformation of TDP-43 metabolism. The controversy, however, is whether or not such pathological protein deposits of RNA binding protein simply reflect a more widespread alteration in RNA metabolism. As we will delineate in this chapter, there is another potential explanation for the pathogenesis of the frontotemporal syndromes of ALS, and more specifically that of ALS with cognitive impairment (ALSci), in that there is also substantive evidence that alterations in tau metabolism are present in ALSci.

Chapter.  3982 words.  Illustrated.

Subjects: Neurology

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