Ask about this productRelated genes to: Tmem106b Blocking Peptide
- Gene:
- TMEM106B NIH gene
- Name:
- transmembrane protein 106B
- Previous symbol:
- -
- Synonyms:
- MGC33727, FLJ11273
- Chromosome:
- 7p21.3
- Locus Type:
- gene with protein product
- Date approved:
- 2005-12-19
- Date modifiied:
- 2014-11-19
Related products to: Tmem106b Blocking Peptide
Related articles to: Tmem106b Blocking Peptide
- TMEM106B, a lysosomal transmembrane protein, is a risk factor for neurodegenerative diseases, including Alzheimer disease (ad) and TDP-43 proteinopathies. TMEM106B pathology occurs in normal aging and is increased in TDP-43 proteinopathy but its role in dementia remains unclear. Cerebrovascular disease (CVD) is a driver and co-pathology of dementia, yet its contribution to TMEM106B accumulation in the context of TDP-43 and ad neuropathological changes (ADNC) has not been explored. We analyzed post-mortem human hippocampal sections spanning not-, low-, intermediate-, and high-ADNC. In secondary analyses, cases ≥65 years were stratified by TDP-43 immunopositivity and CVD severity; cases <65 years were included to contextualize age-associated effects. TMEM106B immunoreactivity was quantified using digital pathology. Linear regression models demonstrated that age and sex (higher in females) were independent predictors of TMEM106B immunopositivity whereas Braak stage, CERAD-NP score, and Thal phase were not. The positive TDP-43-TMEM106B association was attenuated with increased CVD pathology severity, suggesting that vascular burden modifies this relationship. Sensitivity analyses restricted to LATE-NC attenuated several associations, indicating that pooled TDP-43 findings should be interpreted cautiously given possible disease heterogeneity. TMEM106B immunoreactivity was most strongly associated with age and sex, while vascular burden, rather than ADNC level, modified its relationship with TDP-43 proteinopathy. - Source: PubMed
Publication date: 2026/04/17
Dopler Matthew BCorbett ColeGonzalez Angelique DGhaseminejad-Bandpey AliKeating MalloryClarke Kyra MOgunbona Oluwaseun BMaestre GladysSeshadri SudhaEtemadmoghadam ShahrooFlanagan Margaret E - Transmembrane protein 106B (TMEM106B) is a lysosomal glycoprotein whose genetic polymorphisms contribute to the severity of neurodegenerative disorders associated with TDP-43 pathology. Recent studies have revealed that TMEM106B can form amyloid filaments composed of C-terminal fragments (CTFs) in the human brain. In the present study, we explored the relationships between TMEM106B, age, TDP-43, and tau aggregates, and their roles in neurodegeneration. We used immunohistochemistry with an antibody against CTFs of TMEM106B on postmortem human brain fragments (amygdala, hippocampus, temporal cortex, frontal cortex, and basal ganglia) from patients with and without TDP-43/tau pathology at different ages (6-94 years) and with different neurological conditions (subacute sclerosing panencephalitis, Alzheimer's disease, frontotemporal lobar degeneration, and neurologically healthy subjects). Our results revealed that TMEM106B CTF fibrillization is a common, nonspecific, diffuse, and age-dependent phenomenon (appearing after >52 years of age) that affects neurons and neuroglia (most numerous in astrocytes and oligodendrocytes) and broad neuroanatomical regions (most severe in the temporal cortex). We did not find TMEM106B CTF aggregates in young subjects with TDP-43/tau pathology (with subacute sclerosing panencephalitis), but we revealed differences in TMEM106B CTF fibrillization between Alzheimer's disease without TDP-43 pathology, frontotemporal lobar degeneration with TDP-43 pathology, and older healthy subjects without TDP-43/tau pathology. Our results suggest that TMEM106B CTF aggregation is an age-dependent phenomenon and may have a weak association with TDP-43 or tau pathology, shedding new light on the complex relationships among TMEM106B, TDP-43, and tau and the unclear role of TMEM106B fibril formation in the neurodegeneration process. - Source: PubMed
Publication date: 2026/04/06
Acewicz AlbertTarka SylwiaGrzegorczyk MichałRzepliński RadosławWierzba-Bobrowicz TeresaStępień Tomasz - Frailty, a clinical state of increased vulnerability to stressors with aging, imposes significant strain on healthcare systems. Its genetic underpinnings remain incompletely explored, highlighting the need to identify novel therapeutic targets for aging. - Source: PubMed
Publication date: 2026/04/01
Zhong JiaYuYuan MingHaoZhou EnHu Shuo - Frontotemporal dementia (FTD) is the second most common cause of dementia after Alzheimer disease. Mutations in , which encodes progranulin, are a major cause of FTD. Common genetic variants in the gene modify risk of FTD and the effect is especially strong in mutation carriers. Intriguingly, in mutation carriers, being homozygous for the protective haplotype seems to confer near lifetime protection against FTD. Despite the strong genetic link between and , how these two genes interact mechanistically has remained unresolved. Recent studies have revealed that a C-terminal fragment of TMEM106B forms amyloid fibrils and accumulates in the brains of older individuals and patients with neurodegenerative disorders, including FTD. How the production of this fragment connects to granulin deficiency is also unknown. Using lysosome immunoprecipitation, we show that granulin deficiency drives the accumulation of the TMEM106B C-terminal fragment within lysosomes in -knockout mice and -null human iPSC-derived neurons. Recombinant progranulin supplementation reduced TMEM106B C-terminal fragment accumulation. Isogenic neurons carrying the risk allele displayed allele-dose-dependent fragment accumulation that was reversible by progranulin. Structural and genetic analyses demonstrated that TMEM106B dimerization stabilizes the protein and limits C-terminal fragment formation. These findings define a lysosomal pathway linking granulin deficiency to TMEM106B C-terminal fragment accumulation and explain how protective alleles can confer resistance to FTD, even for mutation carriers. - Source: PubMed
Publication date: 2026/03/27
Zeng YiXiong JianLovchykova AnastasiiaNguyen Thao PhuongSong AbigailGitler Semma WAbu-Remaileh MontherGitler Aaron D - Variants in and , which encode lysosomal proteins, interact through unknown mechanisms to increase the risk of age-related cognitive decline and neurodegeneration. Here, we show that these variants converge on a single molecular intermediate: the cleaved intra-lysosomal fibril core of TMEM106B, a precursor to amyloid fibrils that accumulate in the aging brain. A protein-coding risk variant (p.T185) drives fibril core accumulation by impairing its degradation and risk variants amplify this effect. Mice over-expressing the fibril core develop hallmarks of neurodegeneration, and cryo-electron tomography reveals intra-lysosomal fibrils in cultured neurons, mice, and diseased human brain. In -mutation carriers, in whom fibril burden is greatest, fibrils extrude through ruptured lysosomal membranes. These findings identify intra-lysosomal TMEM106B fibrillization as a convergent neurodegeneration mechanism and potential therapeutic target. - Source: PubMed
Publication date: 2026/03/28
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