MAPT (Ab-356) Antibody
Description
Role of p-tau Ser356 in Tau Aggregation
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STA Core Localization: Phospho-Ser356 resides within the seeding-competent tau aggregate (STA) core, which spans residues ~258–368 in tau. This region is critical for early-stage NFT formation .
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Antibody Accessibility: Limited immunodepletion efficiency (~42.7–70.4%) with MTBR-targeting antibodies (e.g., 77G7) suggests Ser356 is partially shielded in the STA core .
Immunohistochemical Profiling
Comparative studies in Braak NFT stages (0–VI) revealed:
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Low Braak Stages (0–II): p-tau Ser356 labels pre-NFTs with granular, vesicle-like staining in pyramidal cell bodies and proximal dendrites (Fig. 3b,g) .
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High Braak Stages (V–VI): Increased confluent staining in neuronal soma and rare neuropil threads .
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Distinct Staining Patterns:
Comparative Analysis of Tau Phospho-Site Antibodies
Table 2 contrasts p-tau Ser356 with other tau phospho-epitopes.
Validation and Applications
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Western Blot: Detects endogenous p-tau Ser356 at ~78 kDa (matching tau’s molecular weight) .
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Immunohistochemistry: Optimal dilution 1:50–1:200; labels early-stage NFTs in hippocampal CA1 neurons .
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Cross-Reactivity: No reported cross-reactivity with non-tau proteins .
Implications for Tauopathy Diagnostics
p-tau Ser356 is a biomarker for early tau aggregation before mature NFT formation. Its detection in granular somatic inclusions suggests utility in identifying pre-tangle pathology, while its limited neuropil thread reactivity distinguishes it from later-stage markers like AT8 .
Product Specs
Target Background
- Genetic manipulation of Sirt3 revealed that amyloid-beta increased levels of total tau and acetylated tau through its modulation of Sirt3. PMID: 29574628
- Data suggest that both the small heat shock protein HspB1/Hsp27 and the constitutive chaperone Hsc70/HspA8 interact with tau to prevent tau-fibril/amyloid formation. Chaperones from different families play distinct but complementary roles in preventing tau-fibril/amyloid formation. (HspB1 = heat shock protein family B small member 1; Hsc70 = heat shock protein family A Hsp70) PMID: 29298892
- A 2.0-kDa peptide that biochemically and immunologically resembles the injected amino terminal tau 26-44 was endogenously detected in vivo, being present in hippocampal synaptosomal preparations from Alzheimer's disease subjects. PMID: 29508283
- A study reports the identification of new bona fide human brain circular RNAs produced from the MAPT locus. PMID: 29729314
- TAU attaches to brain lipid membranes where it self-assembles in a cation-dependent manner. PMID: 29644863
- Microtubule hyperacetylation enhances KL1-dependent micronucleation under a Tau deficiency in mammary epithelial cells. PMID: 30142893
- This article presents key studies of tau in oligodendrocytes and select important studies of tau in neurons. The extensive work on tau in neurons has considerably advanced the understanding of how tau promotes either health or disease. [review] PMID: 30111714
- Zn2+ enhances Tau aggregation-induced apoptosis and toxicity in neuronal cells. PMID: 27890528
- Tau binds to synaptic vesicles via its N-terminal domain and interferes with presynaptic functions. PMID: 28492240
- A study identifies a potential "two-hit" mechanism in which tau acetylation disengages tau from microtubules (MT) and also promotes tau aggregation. Thus, therapeutic approaches to limit tau K280/K281 acetylation could simultaneously restore MT stability and ameliorate tau pathology in Alzheimer's disease and related tauopathies. PMID: 28287136
- In vitro neuroprotective effects of naringenin nanoemulsion against beta-amyloid toxicity through the regulation of amyloidogenesis and tau phosphorylation. PMID: 30001606
- To confirm the neuroprotective role of 24-OH, in vivo experiments were run on mice that express human tau without spontaneously developing tau pathology (hTau mice), by means of the intracerebroventricular injection of 24-OH. PMID: 29883958
- These findings suggest a relatively homogeneous clinicopathological phenotype in P301L MAPT mutation carriers in our series. This phenotype might help in the differential diagnosis from other tauopathies and be a morphological hint for genetic testing. The haplotype analysis results suggest a founder effect of the P301L mutation in this area. PMID: 28934750
- A report indicates that the interaction of Tau with vesicles results in the formation of highly stable protein/phospholipid complexes. These complexes are toxic to primary hippocampal cultures and are detected by MC-1, an antibody recognizing pathological Tau conformations. The core of these complexes is comprised of the PHF6* and PHF6 hexapeptide motifs, the latter in a beta-strand conformation. PMID: 29162800
- A more selective group of neurons appears to be affected in frontotemporal lobar degeneration (FTLD)-TDP and FTLD-FUS than in FTLD-tau. PMID: 28984110
- Our data show that the hyperacetylation of Tau by p300 histone acetyltransferase (HAT) disfavors liquid-liquid phase separation, inhibits heparin-induced aggregation, and impedes access to LLPS-initiated microtubule assembly. PMID: 29734651
- Because neurofibrillary tangles are aberrant intracellular inclusions formed in AD patients by hyperphosphorylated tau, it was initially proposed that phosphorylated and/or aggregated intracellular tau protein was causative of neuronal death. However, recent studies suggest a toxic role for non-phosphorylated and non-aggregated tau when it is located in the brain extracellular space. [review] PMID: 29584657
- MAPT rs242557G/A genetic polymorphism is associated with susceptibility to sporadic AD, and individuals with a GG genotype of rs242557G/A might be at a lower risk. PMID: 29098924
- A study indicates that there are at least two common patterns of TDP-43 and tau protein misfolding in human brain aging. In patients lacking substantial Alzheimer's disease pathology, cerebral age-related TDP-43 with sclerosis (CARTS) cases tend to have tau neurofibrillary tangles in the hippocampal dentate granule neurons, providing a potential proxy indicator of CARTS. PMID: 28281308
- Patients with Kii amyotrophic lateral sclerosis and parkinsonism-dementia complex (Kii ALS/PDC) had dislocated, multinucleated Purkinje cells and various tau pathologies in the cerebellum. These cerebellar abnormalities may provide new insights into the pathomechanism of Kii ALS/PDC and may provide a neuropathological marker for the condition. PMID: 28236345
- The study findings indicate that p.E372G is a pathogenic microtubule-associated protein tau mutation that causes microtubule-associated protein tau similar to p.G389R. PMID: 27529406
- Solvent ionic strength, temperature, and polarity altered tau conformation dynamics. PMID: 29630971
- MAPT alternative splicing is associated with Neurodegenerative Diseases. PMID: 29634760
- High tau expression is associated with blood vessel abnormalities and angiogenesis in Alzheimer's disease. PMID: 29358399
- We identified common splice factors hnRNP F and hnRNP Q regulating the haplotype-specific splicing of MAPT exon 3 through intronic variants rs1800547 and rs17651213. PMID: 29084565
- Cognitive impairment in progressive supranuclear palsy is associated with severity of progressive supranuclear palsy-related tau pathology. PMID: 29082658
- These observations indicate the ability of QUE to decrease tau protein hyperphosphorylation and thereby attenuate the associated neuropathology... these results support the potential of QUE as a therapeutic agent for AD and other neurodegenerative tauopathies. PMID: 29207020
- Increasing microtubule acetylation rescues human tau-induced microtubule defects and neuromuscular junction abnormalities in Drosophila. PMID: 28819043
- The findings reveal the ability of Bin1 to modify actin dynamics and provide a possible mechanistic connection between Bin1 and tau-induced pathobiological changes of the actin cytoskeleton. PMID: 28893863
- We find that both the generation of Abeta and the responsiveness of TAU to A-beta are affected by neuronal cell type, with rostral neurons being more sensitive than caudal neurons. PMID: 29153990
- The results of the current study indicate that variations in microtubule-associated protein tau influence cognition in progressive supranuclear palsy. PMID: 29076559
- The identification of mutations in MAPT, the gene that encodes tau, causing dementia and parkinsonism established the notion that tau aggregation is responsible for the development of disease. PMID: 28789904
- CSF tau proteins and their index differentiated between Alzheimer's disease or other dementia patients and cognitively normal subjects, while CSF levels of neurofilaments expressed as their index seem to contribute to the discrimination between patients with neuroinflammation and normal controls or AD patients. PMID: 28947837
- Comparison of the distributions of tau pTyr18 and double-phosphorylated Syk in the transgenic mouse brain and human hippocampus showed that the phosphorylation of tyrosine 18 in tau already occurs at an early stage of tauopathy and increases with the progression of neurodegeneration. Syk appears unlikely to be a major kinase that phosphorylates tyrosine 18 of tau at the early stage of tauopathy. PMID: 28919467
- A study confirmed that Western diet did not exacerbate tau pathology in hTau mice, observed that voluntary treadmill exercise attenuates tau phosphorylation, and reported that caloric restriction seems to exacerbate tau aggregation compared to control and obese hTau mice. PMID: 28779908
- A study showed a gradual accumulation of nuclear tau in human cells during aging and its general co-localization with the DAPI-positive heterochromatin, which seems to be related to aging pathologies (neurodegenerative or cancerous diseases), where nuclear AT100 decreases drastically, a condition very evident in the more severe stages of the diseases. PMID: 28974363
- Methamphetamine can impair the endoplasmic reticulum-associated degradation pathway and induce neuronal apoptosis through endoplasmic reticulum stress, which is mainly mediated by abnormal CDK5-regulated Tau phosphorylation. PMID: 29705343
- Aha1 colocalized with tau pathology in brain tissue, and this association positively correlated with Alzheimer disease progression. PMID: 28827321
- The subcellular localization of tau45-230 fragment was assessed using tau45-230-GFP-transfected hippocampal neurons, as well as neurons in which this fragment was endogenously generated under experimental conditions that induced neurodegeneration. Results suggested that tau45-230 could exert its toxic effects by partially blocking axonal transport along microtubules, contributing to the early pathology of Alzheimer's disease. PMID: 28844006
- Frontotemporal dementia and parkinsonism linked to chromosome 17 tau with a mutation in the C-terminal region had different banding patterns, indicating a different phosphorylation pattern. PMID: 27641626
- A study demonstrated the presence of the smaller Tau isoform (352 amino acids), whose amount increases in differentiated SK-N-BE cells, with Tau-1/AT8 nuclear distribution related to the differentiation process. PMID: 29684490
- In primary-culture fetal astrocytes, streptozotocin increases phosphorylation of Tau at Ser396. alpha-boswellic acid reduced hyperphosphorylated tau (Ser404). Interruption in astroglial Reelin/Akt/Tau signaling pathways may have a role in Alzheimer disease. PMID: 27567921
- Screening of MAPT, GRN, and CHCHD10 genes in Chinese patients with frontotemporal dementia (FTD) identified about 4.9% mutation carriers. Among the known FTD causative genes tested, MAPT and CHCHD10 play the most important roles in Chinese patients with sporadic FTD. PMID: 28462717
- Data show that aggregation of the Tau protein correlates with destabilization of the turn-like structure defined by phosphorylation of Ser202/Thr205. PMID: 28784767
- Deletion or inhibition of the cytoplasmic shuttling factor HDAC6 suppressed neuritic tau bead formation in neurons. PMID: 28854366
- We propose that the H2 haplotype, which expresses reduced 4R tau compared with the H1 haplotype, may exert a protective effect as it allows for more fluid mitochondrial movement along axons with high energy requirements, such as the dopaminergic neurons that degenerate in PD. PMID: 28689993
- Results find that overexpression of hTau increases intracellular calcium, which in turn activates calpain-2 and induces degradation of alpha4 nAChR. PMID: 27277673
- When misfolded tau assemblies enter the cell, they can be detected and neutralized via a danger response mediated by tau-associated antibodies and the cytosolic Fc receptor tripartite motif protein 21 (TRIM21). PMID: 28049840
- Stress granules and TIA-1 play a central role in the cell-to-cell transmission of Tau pathology. PMID: 27460788
- A clinicopathologic study shows inter- and intra-familial clinicopathologic heterogeneity of FTDP-17 due to MAPT p.P301L mutation, including globular glial tauopathy in one patient. PMID: 27859539
Q&A
What is MAPT (Ab-356) Antibody and what does it target?
MAPT (Ab-356) Antibody is a polyclonal antibody that specifically targets the microtubule-associated protein tau at the Ab-356 epitope. It recognizes tau, which promotes microtubule assembly and stability, and plays a critical role in the establishment and maintenance of neuronal polarity. The antibody binds to the tau protein, which functions as a linker between axonal microtubules (via its C-terminus) and neural plasma membrane components (via its N-terminus) .
What are the validated applications for MAPT (Ab-356) Antibody?
The MAPT (Ab-356) Antibody has been validated for multiple experimental applications including Enzyme-Linked Immunosorbent Assay (ELISA) and Immunofluorescence (IF). It has been tested and confirmed to react with human, mouse, and rat samples, making it versatile for cross-species research in neuroscience and neurodegenerative disease models .
What is the host species and clonality of MAPT (Ab-356) Antibody?
The MAPT (Ab-356) Antibody is a rabbit-derived polyclonal antibody of the IgG isotype. It is provided in an unconjugated form in liquid formulation. The polyclonal nature means it can recognize multiple epitopes of the target protein, potentially increasing sensitivity in certain applications .
How should I optimize immunofluorescence protocols when using MAPT (Ab-356) Antibody?
For optimal immunofluorescence results with MAPT (Ab-356) Antibody, methanol fixation has been validated as shown in HeLa cells . A systematic optimization approach is recommended:
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Begin with a 1:100-1:500 dilution range
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Test different fixation methods (methanol is confirmed effective)
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Include appropriate blocking steps (typically 5-10% normal serum)
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Optimize primary antibody incubation (typically 1-2 hours at room temperature or overnight at 4°C)
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Perform stringent washing steps between incubations
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Use fluorophore-conjugated secondary antibodies specific to rabbit IgG
Comparing your results with the reference images of methanol-fixed HeLa cells available from the manufacturer can help validate your protocol .
How can I integrate MAPT (Ab-356) Antibody into studies of Alzheimer's disease models?
When designing experiments to study Alzheimer's disease using MAPT (Ab-356) Antibody, consider the following approach:
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Select appropriate models that express relevant MAPT haplotypes (H1 or H2), as these have been implicated in differential Alzheimer's disease risk
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Use the antibody in conjunction with markers for amyloid-beta to investigate tau-amyloid interactions
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Consider stratifying samples based on MAPT haplotypes for more nuanced analysis, similar to APOE stratification approaches
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Include controls for different disease stages to track tau pathology progression
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Correlate immunofluorescence findings with cognitive or behavioral data when using animal models
This integrated approach can help reveal associations between tau pathology and disease progression that might be haplotype-dependent .
What are common technical issues with MAPT (Ab-356) Antibody and how can they be resolved?
When working with MAPT (Ab-356) Antibody, researchers may encounter several technical challenges:
| Issue | Possible Causes | Solutions |
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| High background | Insufficient blocking, excessive antibody concentration | Increase blocking time/concentration, titrate antibody, add 0.1-0.3% Triton X-100 in blocking buffer |
| Weak or no signal | Epitope masking, insufficient permeabilization, degraded antibody | Try alternative fixation methods, increase permeabilization time, check antibody storage conditions |
| Non-specific binding | Cross-reactivity with similar epitopes | Perform additional blocking with 5% BSA, include competition assays with recombinant tau |
| Inconsistent results | Batch variation, sample heterogeneity | Use consistent lot numbers, standardize sample preparation |
For all applications, proper storage at -20°C or -80°C is essential to maintain antibody performance .
How can I validate the specificity of MAPT (Ab-356) Antibody in my experimental system?
To confirm MAPT (Ab-356) Antibody specificity in your particular experimental system:
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Perform a Western blot analysis to verify single band detection at the expected molecular weight
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Include a MAPT knockout or knockdown control to confirm signal absence
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Conduct pre-adsorption tests with recombinant tau protein
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Compare staining patterns with other validated tau antibodies targeting different epitopes
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Verify subcellular localization is consistent with known tau distribution (axonal enrichment in neurons)
These validation steps are particularly important when applying the antibody to new experimental models or cell types beyond those already validated (human, mouse, rat) .
How should I quantify and analyze MAPT immunofluorescence data in neurodegeneration studies?
When analyzing MAPT immunofluorescence data in neurodegeneration research:
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Use automated image analysis software with consistent parameters for objective quantification
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Measure both signal intensity and distribution patterns (diffuse vs. aggregated)
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Normalize signals to appropriate internal controls
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Consider co-localization analyses with other markers (e.g., phospho-tau epitopes, microtubules)
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For differential accessibility studies, follow approaches similar to those used in epigenetic research:
When integrating with transcriptomic data, consider analyzing whether differential MAPT expression correlates with accessibility profiles, similar to approaches used in epigenetic studies .
How can I interpret contradictory results between MAPT (Ab-356) Antibody and other tau detection methods?
When facing contradictory results between different tau detection methods:
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Consider epitope-specific differences - the Ab-356 epitope may be differentially accessible in certain tau conformations or post-translational modifications
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Evaluate fixation and sample preparation effects - different detection methods may require different sample preparations
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Assess whether the contradictions reflect biological reality - different tau species may be present in different cellular compartments
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Perform sequential or simultaneous detection with multiple methods to directly compare signals
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Validate findings with functional assays that assess tau activity rather than just presence
Remember that discrepancies between methods often reveal important biological insights rather than technical failures.
How can MAPT (Ab-356) Antibody be utilized in studies of epigenetic influences on tauopathies?
For investigating epigenetic influences on tauopathies with MAPT (Ab-356) Antibody:
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Combine immunofluorescence with chromatin accessibility assays (e.g., ATAC-seq) to correlate tau pathology with epigenetic states
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Integrate with studies of Mendelian disorders of the epigenetic machinery (MDEMs) that may affect tau expression or processing
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Design experiments that examine:
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Differential accessibility of tau-related genes in disease models
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Effects of epigenetic modifiers on tau expression patterns
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Correlation between chromatin states and tau aggregation propensity
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This approach can reveal whether epigenetic mechanisms contribute to tau pathology through altered gene expression or protein processing pathways, similar to methodologies used in mapping functional epigenetic variation in Mendelian disorders .
What are advanced strategies for multiplexing MAPT (Ab-356) Antibody with other neurodegeneration markers?
Advanced multiplexing strategies with MAPT (Ab-356) Antibody include:
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Sequential immunofluorescence with spectral unmixing to overcome antibody host limitations
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Combining with proximity ligation assays to detect tau interactions with binding partners
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Integration with spatial transcriptomics to correlate tau pathology with gene expression patterns
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Mass cytometry approaches for single-cell analysis of multiple markers
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Expansion microscopy to improve spatial resolution when examining tau in neuronal processes
When designing multiplexed experiments, consider careful antibody panel selection to avoid cross-reactivity and spectral overlap, and implement appropriate controls for each marker.
How does MAPT (Ab-356) Antibody performance compare with other tau antibodies in detecting different tau isoforms?
The comparative performance analysis of MAPT (Ab-356) Antibody versus other tau antibodies:
This comparison helps researchers select the most appropriate antibody based on their specific experimental questions and models.
How can MAPT (Ab-356) Antibody be integrated into studies examining MAPT haplotype influences on disease risk?
To integrate MAPT (Ab-356) Antibody into haplotype-focused research:
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Stratify experimental samples by MAPT haplotype (H1 vs. H2) as determined by genotyping the rs8070723 tagging SNP
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Compare antibody binding patterns between haplotype groups to identify potential conformational or expression differences
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Use the antibody in conjunction with transcriptomic analysis to determine if haplotype-specific expression patterns correlate with protein detection
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Design case-control studies with matched haplotypes to control for this variable
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Consider bivariate analysis to assess joint effects of MAPT haplotypes and other genetic factors on antibody-detected tau patterns
This approach parallels APOE-stratified analysis methods in Alzheimer's disease research and may reveal haplotype-specific disease mechanisms .
How might MAPT (Ab-356) Antibody contribute to rapid diagnostic development for tauopathies?
MAPT (Ab-356) Antibody could potentially be adapted for rapid diagnostic applications through:
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Integration into lateral flow assay formats for point-of-care testing
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Development of standardized ELISA protocols with defined cutoffs for pathological tau levels
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Combination with digital biomarker approaches in multiplex panels
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Adaptation for cerebrospinal fluid or blood-based diagnostic platforms
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Correlation with rapid cognitive assessment tools like Acadience to establish predictive validity
Similar to how rapid automatized naming (RAN) tests are used to assess cognitive function , rapid tau detection systems could provide early biomarkers for tauopathy progression.
What are the considerations for using MAPT (Ab-356) Antibody in longitudinal studies of tau pathology?
For longitudinal studies tracking tau pathology:
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Establish baseline measurements with standardized protocols to ensure comparability over time
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Consider stability of the epitope detected by Ab-356 over disease progression
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Implement quality control measures to account for potential lot-to-lot antibody variations
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Create a biobank of control samples to run alongside longitudinal samples
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Develop quantitative metrics that can be consistently applied across timepoints
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Correlate antibody-based measurements with functional or cognitive assessments at each timepoint
This approach enables tracking of tau pathology evolution while maintaining methodological consistency throughout the study duration.
