Neuroinflammation, Calcium Signaling, and Tau Transfer: The Role of FAM84B
A 2026 research article in Journal of Neuroinflammation investigated how inflammatory signaling may influence the movement of tau protein between cells. The study identified FAM84B, also known as LRATD2, as a regulator of tau export and intercellular transfer.
Using human postmortem brain tissue, patient-derived cortical neurons, and experimental cell models, the researchers examined connections among FAM84B expression, inflammatory signaling, and ryanodine receptor-linked intracellular calcium signaling.
Their findings suggest that inflammatory signals can increase FAM84B expression and promote the release of tau into the extracellular environment, where it can subsequently be taken up by neighboring cells. The study investigated this transfer process rather than demonstrating that transferred tau causes progressive disease.
Tau Export and Transfer
Increased FAM84B expression promoted extracellular tau release and transfer to neighboring cells in the experimental systems studied.
Intracellular Calcium Signaling
The findings implicated ryanodine receptor 3-linked calcium signaling in FAM84B-associated tau export and intercellular transfer.
Inflammatory Regulation
IL-6-associated STAT3 activation increased FAM84B expression, providing a mechanistic connection between inflammatory signaling and tau transfer.
FAM84B in Human Tissue and Cellular Models
The researchers detected elevated FAM84B levels in postmortem cortical tissue from several tauopathy groups, including Alzheimer's disease, and in induced pluripotent stem cell-derived cortical neurons from patients with Alzheimer's disease.
In experimental cell models, increasing FAM84B expression promoted the extracellular release of total and phosphorylated tau. These findings support a role for FAM84B in redistributing tau from intracellular compartments toward extracellular release and uptake by other cells.
The human tissue findings were observational and based on small cohorts. They do not establish when FAM84B changes occur during disease or whether increased FAM84B expression causes disease progression.
Calcium Signaling and Tau Release
The study linked FAM84B-associated tau export to ryanodine receptor 3 (RYR3), an intracellular calcium-release channel. The results suggest that calcium-dependent processes contribute to the release and subsequent intercellular transfer of tau in these models.
Treatment with dantrolene, a pharmacological inhibitor of ryanodine receptor signaling, reduced FAM84B- and inflammatory cytokine-associated tau transfer in the experimental systems. This supports the involvement of ryanodine receptor-linked calcium signaling, without establishing an RYR3-specific drug effect or a clinical treatment benefit.
Inflammatory Signals and FAM84B Expression
Treatment with the proinflammatory cytokine interleukin-6 (IL-6) increased STAT3 activation and FAM84B expression. Experiments using a dominant-negative STAT3 mutant supported a role for STAT3 in this response.
Tumor necrosis factor-alpha (TNF-α) treatment was also associated with increased FAM84B expression. Both IL-6 and TNF-α increased intercellular tau transfer in the cell models examined.
Together, these findings support a mechanism through which inflammatory cytokine signaling may influence tau export and transfer through FAM84B-associated pathways.
Extracellular Release and Uptake by Neighboring Cells
The researchers found evidence for an extracellular vesicle-associated component of tau release. Released tau was subsequently taken up by neighboring cells, with clathrin-associated endocytosis contributing to the transfer process.
However, the isolated extracellular fractions were enriched for vesicle-associated markers rather than definitively established as vesicle-specific preparations. The findings therefore do not prove that extracellular vesicles alone account for tau transfer.
What the Study Concluded
The authors identified FAM84B as a potential mechanistic link between neuroinflammatory signaling and intercellular tau transfer. Their results support a model in which inflammatory signals increase FAM84B expression and engage calcium-linked processes that promote tau export and redistribution between cells.
The biological consequences of this transfer remain unresolved. The study did not establish whether transferred tau initiates pathological aggregation, damages recipient cells, or drives progressive tau pathology in living organisms.
These findings provide a basis for further mechanistic research. They do not demonstrate that targeting FAM84B or ryanodine receptor signaling prevents or treats Alzheimer's disease in patients.
Complete Research Paper
Read the complete paper for the experimental methods, human tissue analyses, cellular findings, and discussion of the study's limitations.
Original article:
Yoon G, Park H, et al. FAM84B promotes intercellular tau transfer through exocytic tau export in response to neuroinflammatory signaling. Journal of Neuroinflammation. 2026. Article in Press.
DOI:
10.1186/s12974-026-04069-7
