​Alzheimer's disease (AD) is a complex and heterogeneous disease, both in terms of clinical presentation and progression of cognitive disorders. Molecular imaging using Positron Emission Tomography (PET) enables in vivo detection of amyloid and tau pathologies, the latter being closely associated with the clinical symptoms of AD. The prognostic value of PET imaging of tau pathology on the subsequent progression of cerebral atrophy and cognitive decline has recently been described, and the regional fixation of the radiotracer [¹⁸F]-flortaucipir has made it possible to predict decline in specific brain areas depending on the cognitive domain considered (see Joliot news). Given the topographical information it provides, the longitudinal progression of tau tracer accumulation monitored by PET imaging could be of interest to better understand the spatial and temporal relationships between tauopathy, cortical atrophy progression and cognitive decline over the same time interval.

In this study, researchers explored the longitudinal progression of flortaucipir fixation and cortical atrophy after an average time interval of 2 years, in a cohort of 27 well-characterized AD patients at stages of mild cognitive impairment or mild dementia. Relationships between progression of regional tau load, cortical atrophy, and clinical decline in specific cognitive domains were also analyzed. The authors found an average longitudinal increase in tau tracer retention, with the exception of the lateral temporo-parietal cortex, where paradoxically these values tended on average to decrease. Individual analyses indicate that patients with high initial tau values show a progressive increase in tracer uptake in the frontal lobe, but a decrease in the temporo-parietal cortex and a rapid clinical decline. Cognitive decline is strongly associated with progression of regional cortical atrophy, but weakly related to progression of tau load measured by PET.

These results suggest that PET-tau imaging could identify subjects with a higher initial tau load in the temporo-parietal cortex and a more rapid disease progression. In these patients, a paradoxical decrease in tau tracer binding over time can be observed in certain brain regions, which should be taken into account when considering the use of tau-PET as a tool for monitoring disease progression and response to potential new treatments. This requires careful consideration of the relevant parameters to be studied, focusing for example on the frontal lobes where tracer uptake increases in all patients.

Contact : Julien Lagarde (J.LAGARDE@ghu-paris.fr)

- [¹⁸F]Flortaucipir is the first compound able to assess the density and distribution of tau neurofibrillary tangles (NFT) in adult patients with cognitive impairment.

Legend: Representation of the average progression of cortical tau tracer fixation in Alzheimer's patients after 2 years of follow-up © J.Lagarde et al., Alz.Res.Ther.2023