Tau Imaging Techniques in Neurodegenerative Diseases

Tau imaging has emerged as a transformative approach for in vivo characterisation of tau protein aggregation in a range of neurodegenerative disorders. Pathological accumulation of hyperphosphorylated tau into neurofibrillary tangles correlates closely with neuronal dysfunction and symptom progression, particularly in Alzheimer’s disease and related tauopathies. Positron emission tomography (PET) using specialised radioligands enables regional mapping of tau aggregates and longitudinal monitoring of disease progression. First-generation tracers such as [18F]AV-1451 demonstrated the feasibility of selective binding to paired helical filaments, while revealing challenges of off-target binding related to monoamine oxidase B and iron deposits. Advances in tracer chemistry have yielded next-generation ligands (e.g. [18F]MK-6240, [18F]PI-2620) with improved affinity, selectivity for mixed 3R+4R tau isoforms and faster brain kinetics. Quantitative analysis of PET signals, through kinetic modelling and standardised uptake value ratio approaches, has enhanced the sensitivity of tau imaging for early diagnosis, differential diagnosis of tauopathies, patient stratification in clinical trials and evaluation of therapeutic interventions. Integration with amyloid PET, structural and functional MRI, as well as cerebrospinal fluid assays, further refines disease staging and risk prediction within a precision-medicine framework.

Research from Nature Portfolio

Recent multicentre investigations have demonstrated that cognitively unimpaired individuals who are positive for both amyloid-β plaques and tau neurofibrillary tangles in the medial temporal lobe or temporal neocortex face a markedly increased risk of progressing to mild cognitive impairment within three to five years. Quantitative survival models show that dual PET positivity confers a substantially higher hazard of clinical decline than isolated amyloid positivity or absence of PET pathology. These data underline the prognostic value of tau PET as a biomarker of disease stage and its potential for identifying high-risk subjects for early intervention trials.

Tau Imaging Techniques in Neurodegenerative Diseases publication trend

The graph below shows the total number of articles in tau imaging techniques in neurodegenerative diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Positron emission tomography (PET): A nuclear imaging technique that uses radiolabelled tracers to visualise molecular processes in the living brain.

Tracer: A radioactive compound designed to bind selectively to pathological proteins such as tau, enabling their detection by PET.

Standardised uptake value ratio (SUVR): A semiquantitative measure comparing tracer uptake in target regions to a reference region to assess pathology burden.

Neurofibrillary tangles: Intracellular aggregates of hyperphosphorylated tau protein that disrupt neuronal function in tauopathies.

Off-target binding: Non-specific tracer retention in brain regions due to interactions with proteins or structures other than the intended tau aggregates.

References

1. An autoradiographic evaluation of AV-1451 Tau PET in dementia. Acta Neuropathologica Communications (2016).
2. In vivo quantification of neurofibrillary tangles with [18F]MK-6240. Alzheimer's Research & Therapy (2018).
3. Discovery and preclinical characterization of [18F]PI-2620, a next-generation tau PET tracer for the assessment of tau pathology in Alzheimer’s disease and other tauopathies. European Journal of Nuclear Medicine and Molecular Imaging (2019).
4. Tau PET imaging: present and future directions. Molecular Neurodegeneration (2017).
5. Amyloid and tau PET-positive cognitively unimpaired individuals are at high risk for future cognitive decline. Nature Medicine (2022).
6. Increased Medial Temporal Tau Positron Emission Tomography Uptake in the Absence of Amyloid-β Positivity. JAMA Neurology (2023).
7. Accuracy of Tau Positron Emission Tomography as a Prognostic Marker in Preclinical and Prodromal Alzheimer Disease. JAMA Neurology (2021).