Tau Tracer Binds to TMEM106B in FTLD
A study links off-target binding of the tau imaging agent flortaucipir in frontotemporal lobar degeneration to the lysosomal protein TMEM106B.
Updated on Nov. 5, 2026 in Alzheimer’s
Researchers found that flortaucipir, a tau-PET tracer used to detect mature phosphorylated tau pathology, shows uptake in frontotemporal lobar degeneration cases with phosphorylated TDP-43 that spatially overlaps with TMEM106B deposition. The analysis used tissue from three cognitively normal controls, seven Alzheimer's disease cases, and ten FTLD-TDP cases.
Why it matters
Flortaucipir is used to detect tau pathology, so off-target binding in FTLD-TDP could affect how scans are interpreted in that disease. The findings point to TMEM106B, a protein already genetically and pathologically linked to frontotemporal lobar degeneration, as a possible contributor to the binding.
The study used post-mortem tissue from 3 cognitively normal controls, 7 Alzheimer's disease cases and 10 FTLD-TDP cases, five of each FTLD-TDP type. Colocalization between the fluorescent flortaucipir analog T726 and TMEM106B was most prominent in the choroid plexus, but the report does not establish a causal mechanism for the binding.
The players
Flortaucipir
Flortaucipir is a tau-PET tracer widely used in clinical and research settings to detect mature phosphorylated tau pathology associated with Alzheimer's disease.
TMEM106B
TMEM106B is a lysosomal protein genetically and pathologically linked to frontotemporal lobar degeneration, and it is the focus of the study's proposed explanation for the off-target binding.
The details
Researchers analyzed formalin-fixed, paraffin-embedded hippocampal and limbic sections and used a fluorescent flortaucipir analog, T726, with confocal microscopy to assess where the tracer bound. TMEM106B was observed across all examined subregions in Alzheimer's disease and FTLD-TDP cases, with additional colocalization in hippocampal regions of FTLD-TDP type C cases.
Timeline
• Study findings were published on November 5, 2026.
Diagnostic Scope
Flortaucipir was developed to track tau pathology in Alzheimer's disease, and this finding shows its signal can also appear in frontotemporal lobar degeneration cases with TDP-43 pathology. The overlap with TMEM106B suggests imaging interpretation in FTLD-TDP may need to account for a second source of tracer retention.
For people being evaluated for dementia, the finding means a flortaucipir scan may not always reflect Alzheimer's pathology alone when frontotemporal degeneration is a possibility. Clinicians interpreting these scans may need to consider TDP-43-related pathology before drawing conclusions.
The takeaway
Imaging results depend on understanding what a tracer actually binds to, and this study shows a tau agent can also reveal a lysosomal protein tied to a different disease. Interpreting scans in dementia workups may require accounting for overlapping pathologies rather than assuming a single source of signal.
Further reading
For related context, see our Alzheimer’s coverage.
Source note: This article includes information reported by Nature.
