No interaction between tau and TDP‐43 pathologies in either frontotemporal lobar degeneration or motor neurone disease. Issue 7 (17th November 2014)

• Record Type: Journal Article
• Authors: Robinson, Andrew C.; Thompson, Jennifer C.; Weedon, Lindsey; Rollinson, Sara; Pickering‐Brown, Stuart; Snowden, Julie S.; Davidson, Yvonne S.; Mann, David M. A.
• Is Part Of: Neuropathology & applied neurobiology. Volume 40:Issue 7(2014)
• Page Start: 844
• Page End: 854
• Publication Date: 2014-11-17
• Subjects: Nervous system -- Diseases -- Pathology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/nan.12155
• Languages: English
• ISSNs: 0305-1846

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="nan12155-sec-0001" sec-type="section"> <title>Introduction</title> <p>Frontotemporal lobar degeneration (FTLD) is classified mainly into FTLD‐tau and FTLD‐TDP according to the protein present within inclusion bodies. While such a classification implies only a single type of protein should be present, recent studies have demonstrated dual tau and TDP‐43 proteinopathy can occur, particularly in inherited FTLD.</p> </sec> <sec id="nan12155-sec-0002" sec-type="section"> <title>Methods</title> <p>We therefore investigated 33 patients with FTLD‐tau (including 9 with <italic>MAPT</italic> mutation) for TDP‐43 pathological changes, and 45 patients with FTLD‐TDP (including 12 with hexanucleotide expansion in <italic>C9ORF72</italic> and 12 with <italic>GRN</italic> mutation), and 23 patients with motor neurone disease (3 with hexanucleotide expansion in <italic>C9ORF72</italic>), for tauopathy.</p> </sec> <sec id="nan12155-sec-0003" sec-type="section"> <title>Results</title> <p>TDP‐43 pathological changes, of the kind seen in many elderly individuals with Alzheimer's disease, were seen in only two FTLD‐tau cases – a 70‐year‐old male with exon 10 + 13 mutation in <italic>MAPT</italic>, and a 73‐year‐old female with corticobasal degeneration. Such changes were considered to be secondary and probably reflective of advanced age. Conversely, there was generally only scant tau pathology, usually only within hippocampus and/or entorhinal cortex, in most patients with FTLD‐TDP or MND. The extent of tau pathology in FTLD‐TDP and MND, as with amyloid β protein, may relate to increased age and possession of Apolipoprotein ε4 allele.</p> </sec> <sec id="nan12155-sec-0004" sec-type="section"> <title>Conclusion</title> <p>We find no predilection or predisposition towards an accompanying TDP‐43 pathology in patients with FTLD‐tau, irrespective of presence or absence of <italic>MAPT</italic> mutation, or that genetic changes associated with FTLD‐TDP predispose towards excessive tauopathy. Where the two processes coexist, this is limited and probably causatively independent of each other.</p> </sec> </abstract>