Application: IHC(p), WBClonality: PolyclonalHost: RabbitPurification: SerumReactivity: Mouse, Rat, HumanNeurodegenerative diseases such as Alzheimer's disease and Parkinson's disease have been increasing rapidly and have become a serious social problem. In recent years, new causative genes have been discovered for amyotrophic lateral sclerosis (ALS) and other intractable neurological diseases opening new avenues for research on pathogenesis. It has been suggested that aggregation and accumulation of specific proteins cause neurotoxicity and the formation of lesions, but the onset and progression mechanisms are still unclear. Neuropathological diagnostic and experimental model biomarkers are needed for drug construction, drug discovery, and therapeutic development.Many neurodegenerative diseases such as Alzheimer's disease (AD) show abnormal lesions in which tau is fibrillated with a distribution that strongly correlates with clinical symptoms and disease progression. Tau is a microtubule-associated protein. In adult human brain, 6 tau isoforms are expressed, which are divided into two groups, 3-repeat (3R) and 4-repeat (4R) tau. Tau assembles into insoluble, filamentous, and hyperphosphorylated inclusions in several neurodegenerative diseases. Different tau isoforms accumulate in different neurodegenerative diseases: all 6 tau isoforms in AD, 3R tau isoforms in Pick’s disease, and 4R tau isoforms in cortico-basal degeneration (CBD) and progressive supranuclear palsy (PSP). Therefore, isoform-specific tau antibodies are useful tools for immunohistochemical and biochemical studies of tau species in diseased brains.Currently, a commercial antibody that recognizes 3R tau and 4R tau is widely used for biochemical and histologic analysis. However, tau deposited in AD is extensively deamidated at N279. Our anti-4R tau antibody specifically recognizes 4R tau isoforms regardless of deamidation and strongly stains tau in AD brains.References:1) Spillantini MG, Goedert M. Lancet Neurol. 2013 Jun; 12 (6): 609-22.2) Umeda Y, et al., Neurosci Lett. 2004 Apr 15; 359 (3): 151-4.3) Dan A, Takahashi M, Masuda-Suzukake M, et al. Extensive deamidation at asparagine residue 279 accounts for weak immunoreactivity of tau with RD4 antibody in Alzheimer's disease brain. Acta Neuropathol Comm 2013; 1 : 54.4) Hasegawa M, Watanabe S, Kondo H, et al., 3R and 4R tau isoforms in paired helical filaments in Alzheimer's disease Acta Neuropathologica 2013; Nov 9.5) DeJesus-Hernandez M, et al., Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72: 245-256. 2011. PMID: 219447786) Renton AE, et al., A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72: 257-268, 2011. PMID: 219447797) Mori K, et al., The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science 339: 1335-1338, 2013. PMID: 233930938) Ash PEA, et al., Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron 77: 639-646, 2013. PMID: 234153129) David MA Mann, et al. Dipeptide repeat proteins are present in the p62 positive inclusions in patients with frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9ORF72. Acta Neuropathologica Communications (2013) 1:68. PMID 2425252510) Konno T, et al. C9ORF72 repeat-associated non-ATG-translated polypeptides are distributed independently of TDP-43 in a Japanese patient with c9ALS. Neuropathol Appl Neurobiol. 2014 Oct;40(6):783-8. doi: 10.1111/nan.12157. No abstract available. PMID: 2486167711) Tan RH, et al. Cerebellar neuronal loss in als cases with ATXN2 intermediate repeat expansions. Ann Neurol. 2015 Nov 24. doi: 10.1002/ana.24565. PMID:2659999712) Davidson Y, et al. Neurodegeneration in Frontotemporal Lobar Degeneration and Motor Neurone Disease associated with expansions in C9orf72is linked to TDP-43 pathology and not associated with aggregated forms of dipeptide repeat proteins. Neuropathol Appl Neurobiol. 2015 Nov 5. doi: 10.1111/nan.12292. PMID: 2653830113) Baborie A, et al. Accumulation of dipeptide repeat proteins predates that of TDP-43 in frontotemporal lobar degeneration associated with hexanucleotide repeat expansions in C9ORF72 gene. Neuropathol Appl Neurobiol. 2015 Aug;41(5):601-12. doi: 10.1111/nan.12178. Epub 2015 Apr 30. PMID: 2518584014) Davidson YS, et al. Brain distribution of dipeptide repeat proteins in frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9ORF72. Acta Neuropathol Commun. 2014 Jun 20;2:70. doi: 10.1186/2051-5960-2-70. PMID: 2495078815) Hasegawa M, Arai T, Nonaka T, Kametani F, Yoshida M, Hashizume Y, Beach TG, Buratti E, Baralle F, Morita M, Nakano I, Oda T, Tsuchiya K, Akiyama H. Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Ann Neurol. 2008 Jun 10;64(1):60-70. PubMed: 1854628416) Masuda M, Hasegawa M, Nonaka T, Oikawa T, Yonetani M, Yamaguchi Y, Kato K, Hisanaga S, Goedert M.Inhibition of alpha-synuclein fibril assembly by small molecules: analysis using epitope-specific antibodies.FEBS Lett. 2009 Feb 18;583(4):787-91. doi: 10.1016/j.febslet.2009.01.037. Epub 2009 Feb 4. PMID: 1918355117) Yonetani M, Nonaka T, Masuda M, Inukai Y, Oikawa T, Hisanaga S, Hasegawa M.Conversion of wild-type alpha-synuclein into mutant-type fibrils and its propagation in the presence of A30P mutant.J Biol Chem. 2009 Mar 20;284(12):7940-50. doi: 10.1074/jbc.M807482200. Epub 2009 Jan 21. PMID: 19164293