Tau Imaging in Neurodegenerative Dementia

Many neurodegenerative dementias are associated with the production and misfolding of hyperphosphorylated tau protein. Those primarily of tau pathology are collectively known as tauopathies, the most common being Alzheimer’s disease (AD). In AD, neurofibrillary tangles of hyperphosphorylated tau protein accumulate and spread to different regions of the brain. The location of these tangles matches expected areas of neurodegeneration. Furthermore, the density of the tangles and extent is associated with the severity of neurodegeneration and cognitive impairment. Non-AD tauopathies also show tau pathology matching neurodegeneration regions, confirming the significant role tau plays in these disorders. Specific PET tracers target the accumulation of pathological misfolded tau allowing investigation into the onset and progression of dementia. The FDA has recently approved the first tau tracer, 18F-flortaucipir, for clinical evaluation of AD. Development of next-generation tau tracers to improve off-target binding and increase binding affinity is currently underway. Tau PET tracers may pave the way for a more accurate diagnosis of not just AD but other tauopathies, serving as both disease staging tools and imaging biomarkers in clinical trials testing anti-tau therapies.