Alzheimer’s disease is one of a family of neurodegenerative disorders called tauopathies, which as the name suggests are defined by the presence of pathological aggregates of the tau protein. Tau has consequently become the focus of efforts to develop targeted therapies that will reverse or remove these aggregates. However, as yet only one drug has reached phase III clinical trials. In the Alzheimer’s Research & Therapy special series ‘Tau-based therapeutic strategies‘ leading researchers in the field take stock of current tau-based approaches and discuss the potential of future therapies. In this podcast, series contributors – John Morris, Chad Dickey and Melissa Murray – talk about the most exciting studies at the moment, from clinical trials to neuroimaging, as well as what they think are the most promising future directions. A full transcript of this podcast can be viewed here.
“If we’re going to be able to diagnose patients only after they start to have clinical symptoms, we may want to try to target something that’s further downstream in the disease process. Tau is such a target; it’s thought to start after amyloid beta starts to aggregate.”
Chad Dickey, University of South Florida
Chad Dickey is an Assistant Professor in the Department of Molecular Medicine at the University of South Florida, USA. He received his PhD in pharmacology and neuroscience at the University of South Florida, under the guidance of David Morgan, after which he joined the Mayo Clinic, USA. His current research interests focus on the molecular mechanisms involved in protein turnover and degradation in the brain, with particular emphasis on the role of molecular chaperones in tauopathies. In this podcast Dickey highlights some of the major players in tau-targeted drugs, as well as explaining why combination therapies involving chaperone inhibitors provide a promising avenue of investigation. More on tau aggregation inhibitors and tau chaperone modulators can be found in a review article by Dickey and colleagues.
“If we had the combined effort of MRI with amyloid imaging or with tau imaging, it would really help to hone down who the patient is so that we can give them whatever therapeutic aspects may be useful, depending on the underlying disease.”
Melissa Murray, Mayo Clinic
Melissa Murray is Assistant Professor of Neuroscience at the Mayo Clinic, USA, whose primary research interests address the clinicopathologic, genetic, and neuroimaging aspects of aging and neurodegenerative diseases. Research in the Murray lab centres on the clinicopathologic differentiation of atypical Alzheimer’s disease (AD), the genetics of atypical Alzheimer’s disease, and the genetics of frontotemporal lobar degeneration. Here Murray discusses how progress in neuroimaging metholodogies can aid the treatment of patients with tauopathies through a better understanding of the disease pathology. Murray and colleagues examine this further in their review article on assessing and imaging tauopathies in neurodegenerative dementias.
“We can now identify preclinical Alzheimer’s disease in cognitively normal older adults. The major question is: what transitions that preclinical stage into the symptomatic stage? What are the triggers that cause that?”
John Morris, Washington University
John Morris is Professor of Neurology at Washington University, USA, and Program Director and Principal Investigator for the international study DIAN – the Dominantly Inherited Alzheimer Network. We hear from Morris about what families with a known pathogenic mutation for Alzheimer’s disease can tell us about the disease pathology and how studies such as DIAN can led to preventative interventions – as further discussed in a review article by Morris and colleagues.
More on tau-based therapeutics, including contributions from Morris, Murray, and Dickey, as well as insights into the propagation of tau pathology and tau acetylation, can be found in the Alzheimer’s Research & Therapy special series linked below.
Interviews conducted by Kathyrn Smith, in-house Editor for Alzheimer’s Research & Therapy.
The complete list of series articles: