For the best experience on the Abcam website please upgrade to a modern browser such as Google Chrome

Hello. We're improving abcam.com and we'd welcome your feedback.

Hello. We're improving abcam.com and we'd welcome your feedback.

Infomation icon

We haven't added this to the BETA yet

New BETA website

New BETA website

Hello. We're improving abcam.com and we'd welcome your feedback.

Take a look at our BETA site and see what we’ve done so far.

Switch on our new BETA site

Now available

Search and browse selected products

  • A selection of primary antibodies

Purchase these through your usual distributor

In the coming months

  • Additional product types
  • Supporting content
  • Sign in to your account
  • Purchase online
United States
Your country/region is currently set to:

If incorrect, please enter your country/region into the box below, to view site information related to your country/region.

Call (888) 77-ABCAM (22226) or contact us
Need help? Contact us

  • My account
  • Sign out
Sign in or Register with us

Welcome

Sign in or

Don't have an account?

Register with us
My basket
Quick order
Abcam homepage

  • Research Products
    By product type
    Primary antibodies
    Secondary antibodies
    ELISA and Matched Antibody Pair Kits
    Cell and tissue imaging tools
    Cellular and biochemical assays
    Proteins and Peptides
    By product type
    Proteomics tools
    Agonists, activators, antagonists and inhibitors
    Cell lines and Lysates
    Multiplex miRNA assays
    Multiplex Assays
    By research area
    Cancer
    Cardiovascular
    Cell Biology
    Epigenetics
    Metabolism
    Developmental Biology
    By research area
    Immunology
    Microbiology
    Neuroscience
    Signal Transduction
    Stem Cells
  • Customized Products & Partnerships
    Customized Products & Partnerships

    Customized products and commercial partnerships to accelerate your diagnostic and therapeutic programs.

    Customized products

    Partner with us

  • Support
    Support hub

    Access advice and support for any research roadblock

    View support hub

    Protocols

    Your experiments laid out step by step

    View protocols

  • Events
    • Conference calendar
    • Cancer
    • Cardiovascular
    • Epigenetics & Nuclear signaling
    • Immunology
    • Neuroscience
    • Stem cells
    • Tradeshows
    • Scientific webinars
    Keep up to date with the latest events

    Full event breakdown with abstracts, speakers, registration and more

    View global event calendar

  • Pathways
    Cell signalling pathways

    View all pathways

    View all interactive pathways

Beta-amyloid and tau in Alzheimer's disease

Related

  • Neuroscience poster library
    • Neuroinflammation and Alzheimer's poster
      • Alzheimer's disease interactive pathway
        • Alzheimer's disease, antibodies, tools and support

          ​​Explore beta-amyloid and tau in Alzheimer's disease and access the tools you need to better understand the role they play within this complex condition.  

          Healthy amyloid precursor protein (APP) is cleaved to pathogenic beta-amyloid (Aβ) peptides through the sequential action of β- and γ-secretases. Similarly, tau protein is hyperphosphorylated by GSK3 and other kinases to first form paired helical filaments and subsequently neurofibrillary tangles (NFTs).

          Here you can find an overview of beta-amyloid and tau, including their functions and structures, as well as find the antibodies and kits you need for your Alzheimer's disease research.

          ​​​​Contents

          • Beta-amyloid in Alzheimer's disease
            ​
            • APP processing
            • Conformational variation
            • Conformation-specific amyloid beta antibodies
          • Tau in Alzheimer's disease
            ​
            • Function of tau
            • Structure of tau
            • Role of tau in Alzheimer's disease
            • Antibodies and kits for tau research
              • ​Tau (phospho T217) product highlight
          • References

          ​​Beta-amyloid in Alzheimer's disease

          ​Alzheimer's disease is characterized by the presence of neurotoxic Aβ plaques in the brain. These plaques are formed by monomeric Aβ spontaneously assembling into soluble oligomers, which cluster together to form insoluble fibrils. Evidence suggests a role for both soluble oligomers and insoluble fibrils in Alzheimer’s disease pathology, but their exact contributions are still under debate. Here we cover the generation of Aβ from APP and how structural variation of Aβ may explain the complex pathology of Alzheimer’s disease.

          APP processing

          Pathogenic Aβ peptides are produced by the proteolytic cleavage of APP by enzyme complexes β- and γ-secretases. APP cleavage occurs via two distinct pathways (Figure 1). The non-amyloidogenic pathway provides beneficial neurotrophic effects and the amyloidogenic pathway produces neurotoxic Aβ peptides. The Aβ peptides formed via the amyloidogenic pathway can misfold and aggregate into deposits that contribute to Alzheimer’s disease pathology.

          ​​​​​Figure 1. The non-amyloidogenic and amyloidogenic pathways of APP processing.

          The non-amyloidogenic pathway

          The non-amyloidogenic pathway involves cleavage of APP by α-secretase to generate two fragments: an 83 amino acid C-terminal fragment (C83) that remains in the membrane and an N-terminal ectodomain (sAPPα) that is released into the extracellular medium.

          Three enzymes have been identified with α-secretase activity: ADAM9, ADAM10, and ADAM171. Importantly, cleavage of APP by α-secretase occurs within the Aβ domain and consequently prohibits Aβ peptide production.

          Of note, the C83 membrane fragment can be subsequently cleaved by γ-secretase to produce a short fragment called P3 peptide and an APP intracellular domain (AICD). To date, the P3 peptide is believed to be pathologically irrelevant2.

          The amyloidogenic pathway

          The amyloidogenic pathway leads to neurotoxic Aβ generation. β-secretase (BACE1) mediates the first proteolysis step, which releases a large N-terminal ectodomain (sAPPβ) into the extracellular medium. A 99-amino acid C terminal fragment (C99) remains in the membrane3–5.

          The newly exposed C99 N-terminus corresponds to the first amino acid of Aβ. Successive cleavage of this fragment by γ-secretase (between residues 38 and 43) releases the Aβ peptide. γ-secretase is a complex of enzymes consisting of presenilin 1 or 2 (PS1 and PS2), nicastrin, anterior pharynx defective (APH-1) and presenilin enhancer 2 (PEN2) 6–10.

          Most of the Aβ peptides are 40 residues in length (Aβ 1–40), with a small percentage containing 42 residues (Aβ 1–42). Aβ 1–42 is considered the more neurotoxic form because the extra two amino acids provide a greater tendency to misfold and subsequently aggregate11. Elevated plasma levels of Aβ 1–42 have been correlated with Alzheimer’s disease12.

          BACE inhibitors

          Targeting Aβ accumulation by inhibiting its production is important to slow down the progression of Alzheimer’s disease. Blocking APP cleavage is made possible due to access to several β-secretase inhibitors.

          Table 1. Commonly used inhibitors targeting β-secretase and Aβ production.

          Small molecule

          Activity

          abID

          β-Secretase Inhibitor II (Z-VLL-CHO)

          Peptidyl β-secretase inhibitor (reversible). Corresponds to the VNL-DA cleavage site on APP13.

          ab146640

          AZD3839

          Potent and selective BACE-1 inhibitor (Ki = 26.1 nM), about 14-fold selectivity over BACE-2 (Ki = 372 nM)14.

          ab223887

          Lanabecestat (AZD3293)

          Highly potent BACE-1 inhibitor with IC50 = 610 pM (primary neuron cultures from mice), 310 pM (primary neuron cultures from guinea pigs), and 80 pM (SH-SY5Y cells over-expressing AβPP)15.

          ab223888

          Loganin

          Selective β-secretase inhibitor. Shows neuroprotective effects against Aβ(25-35)-induced cell death16.​​

          ab143653

          LY2886721

          Potent and selective BACE-1 inhibitor (IC50 = 20.3 nM for recombinant hBACE-1)17.

          ab223886

          Nilvadipine

          Potent Ca2+ channel blocker that promotes Aβ clearance from the brain and reduced tau hyperphosphorylation18.​​

          ab141311

          Verubecestat (MK-8931)

          Selective, potent β-secretase 1 inhibitor (IC50 = 13 nM)19.

          ab223883

          ​​
          Table 2. Recommended tools to study Aβ in Alzheimer's disease.

          Target

          Tools

          Beta-amyloid

          Beta-amyloid peptide (1–42, human)

          Near-infrared fluorescent Aβ probes

          Conformation-specific amyloid beta antibodies

          See all beta-amyloid products

          β-secretase

          Anti-BACE1 antibody

          β-secretase activity assay kit

          See all β-secretase products

          Conformational variation of beta-amyloid

          One barrier to understanding the role of Aβ in Alzheimer’s disease is the lack of correlation between Aβ in the brain and the cognitive ability of patients. For example, some patients with Aβ deposits show no symptoms of Alzheimer’s disease at all20,21.

          The answer to Alzheimer’s disease heterogeneity may lie in structural variations of Aβ, which can form polymorphic Aβ oligomers in a process known as segmental polymorphism. This is where the segments that form beta sheets vary between different fibril structures22–24.

          Therefore, like in prion diseases, unique forms of structurally distinct Aβ might be deposited in different places and at different times in the brains of patients with Alzheimer’s disease. However, it remains unclear which types of deposit are more closely linked with the cognitive symptoms of the disease25.

          The need for conformation-specific antibodies

          With increasing evidence to support the biomedical importance of Aβ structural variation, conformation-specific Aβ imaging reagents will play a central role in the future of Alzheimer’s research.

          Research in humans has shown the clinical relevance of Aβ structural variation. Tissue taken from two Alzheimer’s disease patients with distinct clinical histories revealed that each patient had a predominant Aβ fibril structure; however, the dominant structure was different in each patient26.

          Studies in mice and cultured cells have also supported the biological relevance of Aβ structural variation. Structurally distinct Aβ fibrils cause varying levels of toxicity in neuronal cultures, while mice given Aβ from different sources develop distinct patterns of Aβ deposition within the brain27,28.

          Furthermore, the complexity of Aβ structure is convincingly reflected by the immune system, with research showing that the antibodies produced in response to Aβ fibrils are diverse, reflecting their structural variation25,29.

          Considering all evidence, it is becoming increasingly clear that a single antibody will not be enough to study or target all the possible pathological aggregates of Aβ contributing to Alzheimer’s disease. This makes conformation-specific Aβ antibodies an essential tool for the future of Alzheimer’s disease research30–33.

          ​​Conformation-specific amyloid beta antibodies

          In collaboration with Professor Charles Glabe (UC Irvine), we developed rabbit monoclonal antibodies against Aβ 1–42 fibrils that can distinguish conformational variation in amyloid structures.

          • Human Aβ (1–42) fibril immunogen
          • Rabbit monoclonal antibodies for high affinity and specificity
          • Validated using dot blot and IHC-P
          • Published in The Journal of Biological Chemistry

          Table 3. Antibody reactivity in human and mouse Alzheimer's disease brain.

          Antibody name

          Antibody ID

          Human Alzheimer's brain specificity shown by IHC**

          Alzheimer's mouse model* brain specificity shown by IHC**

          Anti-amyloid fibril antibody [mOC22] - conformation-specific

          ab205339

          Frontal cortex plaques

          Layer V cortical and CA1 pyramidal neurons

          Anti-beta amyloid 1-42 antibody [mOC23] - conformation specific 

          ab205340

          Subset of frontal cortex plaques

          Hippocampal plaques

          Anti-beta amyloid 1-42 antibody [mOC31] - conformation-specific

          ab201059

          Vascular amyloid deposits

          N/A

          Anti-beta amyloid 1-4 antibody [mOC64] - conformation-specific

          ab201060

          Frontal cortex plaques

          N/A

          Anti-amyloid fibril antibody [mOC78] - conformation specific

          ab205341

          Intracellular/nuclear, frontal cortex plaques

          Layer V cortical neurons

          Anti-amyloid fibril antibody [mOC87] - conformation-specific

          ab201062

          Frontal cortex plaques

          Layer V cortical neurons (intracellular deposits)

          Anti-beta amyloid 1-42 antibody [mOC98] - conformation-specific

          ab201061

          Frontal cortex plaques

          Layer V cortical neurons (intracellular deposits)

          Anti-amyloid fibril antibody [mOC116] - conformation specific

          ab205342

          Frontal cortex plaques

          Layer V cortical neurons, ​hippocampal plaques​

          *14 month-old 3xTg-AD mouse model of Alzheimer's disease
          ** IHC shown in Hatami et al. 2014

          • Browse all conformation-specific Aß antibodies

          Tau in Alzheimer's disease

          A brief introduction to the tau protein and how it contributes to Alzheimer's disease.

          Function of tau

          Under normal circumstances, tau is a microtubule-associated protein (MAP) involved in microtubule stabilization. However, it is also a multi-functional protein with a critical role in certain neurodegenerative disorders including Alzheimer's disease34.

          The tau protein is highly soluble, expressed in neurons, oligodendrocytes, and astrocytes within the central nervous system (CNS) and peripheral nervous system (PNS)35,36.

          Tau is primarily found in axons where it regulates microtubule polymerization and stabilization. However, its broad selection of binding partners suggests that it has multiple functions, including postnatal brain maturation, regulation of axonal transport and signaling cascades, cellular response to heat shock, and adult neurogenesis37.​​

          Structure of tau

          Tau can be divided into four regions: an N-terminal region, a proline-rich domain, a microtubule-binding domain (MBD), and a C-terminal region38.  The human tau gene (MAPT) contains 16 exons, and alternative splicing of exons 2, 3, and 10 yields six isoforms (Figure 2).

          The tau protein contains 85 potential serine (S), threonine (T), and tyrosine (Y) phosphorylation sites, and under normal conditions, phosphorylation helps to maintain the cytoskeletal structure39.  Abnormal phosphorylation of tau is known to contribute to Alzheimer's disease pathology, with approximately 45 specific phosphorylation sites identified in the Alzheimer's disease brain39,40.

          In addition to phosphorylation, tau undergoes multiple post-translational modifications, including glycosylation, glycation, truncation, nitration, oxidation, polyamination, ubiquitination, SUMOylation and aggregation41.

          ​​Figure 2. Alternative splicing of tau produces isoforms ranging in length from 352 to 441 amino acids. Exons 2 and 3 of the tau gene encode two N terminal inserts (N1 and N2). Absence of exons 2 and 3 gives rise to 0N tau isoforms, the inclusion of exon 2 results in 1N isoforms and inclusion of both exons 2 and 3 produces 2N isoforms. R1–R4 represent the four microtubule-binding domains with R2 being encoded by exon 10. Inclusion of exon 10 results in 4R isoforms, while exclusion results in 3R isoforms.​

          Role of tau in Alzheimer's disease

          Accumulation of plaques and intracellular NFTs (Figure 3) is correlated with Alzheimer's disease symptoms and results in neuron damage and death42.  It is now believed that soluble Aβ and tau work in tandem, independently of their accumulation into plaques and tangles, to push neurons towards a diseased state42.​​

          Figure 3. Formation of neurofibrillary tangles (NFTs) by the tau protein in tauopathies such as Alzheimer’s disease. Under pathological conditions, tau becomes hyperphosphorylated and detaches from microtubules. Phosphorylated tau then aggregates to form paired helical filaments (PHFs) and NFTs.

          In Alzheimer’s disease, the elevation of intracellular soluble Aβ leads to the abnormal phosphorylation of tau and its release from microtubules in a soluble monomeric form39,43.  In response to Aβ, tau is relocated from axons to the somatodendritic compartments of neurons43.  Here, tau can bind and sequester the Src tyrosine kinase, fyn, altering its localization44.

          Elevated levels of fyn accompany the elevated levels of tau in dendritic spines, allowing the phosphorylation and stabilization of excitatory GluN2B NMDA receptors. This enhances glutamate signaling and causes an intracellular flood of Ca2+, which enhances Aβ toxicity42,44,45.  Calcium-induced excitotoxicity can damage post-synaptic sites and cause mitochondrial Ca2+ overload, membrane depolarization, oxidative stress and apoptotic cell death42,46,47.

          Extracellular vesicles may be involved in the dissemination of pathological Aβ and tau in a prion-like propagation of Alzheimer's disease plagues and NFTs48,49.

          Novel therapeutic strategies for the treatment of Alzheimer's disease may include preventing the Aβ-induced, tau-dependent enhancement of NMDA receptor activity, by reducing dendritic levels of fyn18 or targeting tau directly50.

          ​​

          ​​

          ​​​​Antibodies and kits for tau research

          Study tau from every angle with a comprehensive array of research tools to get new insights into tau pathology. From aggregation inhibitors to kits and antibodies, find everything you need to untangle tau, in one place.

          Total tau detection

          Tau is found in soluble form in the normal brain but in Alzheimer's disease, becomes aggregated and insoluble. Easily detect total tau with bovine serum albumin (BSA) and azide-free antibody, an antibody panel, or an ELISA kit from the table below.

          Table 4. Tools to detect total tau.

          Reagent

          Recommended product

          abID

          Total tau antibody

          Anti-Tau antibody [TAU-5] - BSA and Azide free

          ab80579

          Conformation specific tau antibody

          Anti-tau Alzheimer's disease antibody [GT-38] - Conformation Specificab246808

          Tau antibody panel

          Tau Research Antibody Panel

          ab226492

          ELISA

          Human Tau ELISA Kit

          ab210972

          Note: Studying insoluble tau can be problematic, consider using detergents such as RIPA and Sarkosyl.53

          Tau phosphorylation

          Tau function is governed by phosphorylation, which becomes dysregulated during pathology, resulting in mislocalization, aggregation, and neuronal death. Effortlessly study all aspects of tau phosphorylation with antibodies against different post-translationally modified sites.

          Tau (phospho T217) product highlight



          ​​

          Recombinant Anti-Tau (phospho T217) antibody [EPR24654-24] (ab288160)

          Rabbit monoclonal to Tau (phospho T217)

          Suitable for: Dot blot, ELISA

          Reacts with: Human

          A carrier-free version of this antibody is also available. 

          Table 5. Tools to study tau phosphorylation.

          Phosphorylation site

          Recommended product

          abID

          Serine 202 and threonine 205

          Anti-Tau (phospho S202 + T205) antibody [EPR20390]

          ab210703

          Threonine 231

          Anti-Tau (phospho T231) antibody [EPR2488]

          ab151559

          Serine 262

          Anti-Tau (phospho S262) antibody

          ab64193

          Serine 396

          Anti-Tau (phospho S396) antibody [EPR2731]

          ab109390

          Serine 422

          Anti-Tau (phospho S422) antibody [EPR2866]

          ab79415

          Browse all antibodies to detect phosphorylated tau.

          If you need multiple phosphorylated tau antibodies, try our Tau antibody panel (ab226492).

          Tau aggregation inhibitors

          The presence of aggregated tau corresponds with pathology in diseases such as Alzheimer’s. Effectively inhibit the formation of neurofibrillary tangles with a potent tau aggregation inhibitor.

          Table 6. Tau inhibitors.

          Small molecule

          Activity

          abID

          TRx0237 mesylate (LMTX)

          Reduces tau pathology and reverses behavioral impairment in mice. Active in vitro and in vivo52.​​

          ab223882

          AZD2858

          Selective GSK-3 inhibitor (IC50 = 68 nM) of tau phosphorylation at the S396 site53.​​

          ab223889

          INDY

          ATP-competitive DYRK1A/B inhibitor capable of reversing tau phosphorylation54.​​

          ab223890

          GSK-3β Inhibitor VII

          Cell-permeable, non-ATP competitive GSK-3β inhibitor
          (IC50 = 0.5 µM) 55.

          ab145937

          YM-01 (YM-1)

          Allosteric Hsp70 modulator which potently reduces aberrant tau levels (EC50 ~ 0.9 μM)56.

          ab146423

          Browse all tau inhibitors

          Browse microtubule activators and inhibitors

          Tau and neuroinflammation

          There is a complex interplay between misfolded proteins and neuroinflammation in neurodegenerative disease.

          Table 7. Tools to study tau in the context of neuroinflammation.

          Tool

          Recommended product(s)

          abID

          Mouse and human multiplex cytokine panels

          Human Key cytokines (17 plex) Multiplex Immunoassay Panel

          Mouse Key cytokines (17 plex) Multiplex Immunoassay Panel

          ab243549​


          ​ab235656

          TNF alpha ELISA kit

          Mouse TNF alpha ELISA Kit

          ab208348

          IL-1 beta ELISA kit

          Mouse IL-1 beta ELISA Kit (Interleukin-1 beta)

          ab100704

          IL-6 ELISA kit

          Human IL-6 ELISA Kit (Interleukin-6) High Sensitivity

          ab46042

          • Get results in 90 minutes - discover the range of SimpleStep ELISA® kits

          References

          1. Allinson, T. M. J., Parkin, E. T., Turner, A. J. & Hooper, N. M. ADAMs Family Members As Amyloid Precursor Protein α-Secretases. J. Neurosci. Res. 74, 342–352 (2003). doi:10.1002/jnr.10737

          2. Haass, C., Kaether, C., Thinakaran, G. & Sisodia, S. Trafficking and proteolytic processing of APP. Cold Spring Harb. Perspect. Med. 2, a006270 (2012). doi:10.1101/cshperspect.a006270

          3. Hussain, I. et al. Identification of a novel aspartic protease (Asp 2) as β-secretase. Mol. Cell. Neurosci. 14, 419–427 (1999). doi:10.1006/mcne.1999.0811

          4. Sinha, S. et al. Purification and cloning of amyloid precursor protein β-secretase from human brain. Nature 402, 537–540 (1999). doi:10.1038/990114

          5. Vassar, R. et al. β-Secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286, 735–741 (1999). doi:10.1126/science.286.5440.735

          6. Francis, R. et al. aph-1 and pen-2 are required for Notch pathway signaling, γ-secretase cleavage of βAPP, and presenilin protein accumulation. Dev. Cell. 3:85–97 (2002). doi:10.1016/S1534-5807(02)00189-2

          7. Levitan, D. et al. PS1 N- and C-terminal fragments form a complex that functions in APP processing and Notch signaling. PNAS. 98, 12186–12190 (2001). doi:10.1073/pnas.211321898

          8. Steiner, H. et al. PEN-2 is an integral component of the γ-secretase complex required for coordinated expression of presenilin and nicastrin. J. Biol. Chem. 277, 39062–39065 (2002). doi:10.1074/jbc.C200469200

          9. Wolfe, M. S. et al. Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity. Nature 398, 513–517 (1999). doi:10.1038/19077

          10. Yu, G. et al. Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and βAPP processing. Nature 407, 48–54 (2000). doi:10.1038/35024009

          11. Ahmed, M. et al. Structural conversion of neurotoxic amyloid-Β 1-42 oligomers to fibrils. Nat. Struct. Mol. Biol. 17:561–567 (2010). doi:10.1038/nsmb.1799

          12. Mayeux, R. et al. Plasma amyloid β-peptide 1-42 and incipient Alzheimer’s disease. Ann. Neurol. 46, 412–416 (1999). doi:10.1002/1531-8249(199909)46:3<412::AID-ANA19>3.0.CO;2-A

          13. Coppola, J. M. et al. Identification of inhibitors using a cell-based assay for monitoring Golgi-resident protease activity. Anal. Biochem. 364, 19–29 (2007). doi:10.1016/j.ab.2007.01.013

          14. Jeppsson, F. et al. Discovery of AZD3839, a potent and selective BACE1 inhibitor clinical candidate for the treatment of Alzheimer’s disease. J. Biol. Chem. 287, 41245–57 (2012). doi:10.1074/jbc.M112.409110

          15. Eketjäll, S. et al. AZD3293: A novel, orally active BACE1 inhibitor with high potency and permeability and markedly slow off-rate kinetics. J. Alzheimer’s Dis. 50, 1109–23 (2016). doi:10.3233/JAD-150834

          16. Kim, H. et al. Neuroprotective effect of loganin against Aβ25-35-induced injury via the NF-κB-dependent signaling pathway in PC12 cells. Food Funct. 6, 1108–16 (2015). doi:10.1039/c5fo00055f

          17. May, P. C. et al. The potent BACE1 inhibitor LY2886721 elicits robust central Aβ  pharmacodynamic responses in mice, dogs, and humans. J. Neurosci. 35, 1199–1210 (2015). doi:10.1523/jneurosci.4129-14.2015

          18. Paris, D. et al. The spleen tyrosine kinase (Syk) regulates Alzheimer amyloid-β production and Tau hyperphosphorylation. J. Biol. Chem. 289, 33927–44 (2014). doi:10.1074/jbc.M114.608091

          19. Yan, R. Stepping closer to treating Alzheimer’s disease patients with BACE1 inhibitor drugs. Transl. Neurodegener. 5, 13 (2016). doi:10.1186/s40035-016-0061-5

          20. Castellani, R. J., Lee, H. G., Zhu, X., Perry, G. & Smith, M. A. Alzheimer disease pathology as a host response. J. Neuropathol. Exp. Neurol. 67, 523–31 (2008).  doi:10.1097/NEN.0b013e318177eaf4

          21. Knopman, D. S. et al. Neuropathology of cognitively normal elderly. J. Neuropathol. Exp. Neurol. 62, 1087–1095 (2003). doi:10.1093/jnen/62.11.1087

          22. Schütz, A. K. et al. Atomic-resolution three-dimensional structure of amyloid b fibrils bearing the osaka mutation. Angew. Chem. Int. Ed. Engl. 54, 331–335 (2015). doi:10.1002/anie.201408598

          23. Tycko, R. Amyloid polymorphism: structural basis and neurobiological relevance. Neuron. 86, 632–645 (2015). doi:10.1016/j.neuron.2015.03.017

          24. Xiao, Y. et al. Aβ(1-42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer’s disease. Nat. Struct. Mol. Biol. 22, 499–505 (2015). doi:10.1038/nsmb.2991

          25. Hatami, A., Albay, R., Monjazeb, S., Milton, S. & Glabe, C. Monoclonal antibodies against Aβ42 fibrils distinguish multiple aggregation state polymorphisms in vitro and in Alzheimer disease brain. J. Biol. Chem. 289, 32131–32143. (2014). doi:10.1074/jbc.M114.594846

          26. Lu, J. X. et al. Molecular structure of β-amyloid fibrils in Alzheimer’s disease brain tissue. Cell 154, 1257–1268 (2013). doi:10.1016/j.cell.2013.08.035

          27. Petkova, A. T. et al. Self-propagating, molecular-level polymorphism in Alzheimer’s β-amyloid fibrils. Science 307, 262–265 (2005). doi:10.1126/science.1105850

          28. Meyer-Luehmann, M. et al. Exogenous induction of cerebral β-amyloidogenesis is governed by agent and host. Science 313, 1781–1784 (2006). doi:10.1126/science.1131864

          29. Pensalfini, A. et al. Intracellular amyloid and the neuronal origin of Alzheimer neuritic plaques. Neurobiol. Dis. 0, 53–61 (2014). doi:10.1016/j.nbd.2014.07.011

          30. Kayed, R. et al. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300, 486–489 (2003). doi:10.1126/science.1079469

          31. Kayed, R. et al. Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers. Mol. Neurodegener. 2, 18 (2007). doi:10.1186/1750-1326-2-18

          32. Kayed, R. et al. Annular protofibrils area structurally and functionally distinct type of amyloid oligomer. J. Biol. Chem. 284, 4230–4237 (2009). doi:10.1074/jbc.M808591200

          33. Kayed, R. et al. Conformation dependent monoclonal antibodies distinguish different replicating strains or conformers of prefibrillar Aβ oligomers. Mol. Neurodegener. 5, 57 (2010). doi:10.1186/1750-1326-5-57

          34. Ballatore, C., Lee, V. M.-Y. & Trojanowski, J. Q. Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat. Rev. Neurosci. 8, 663–672 (2007) doi: 10.1038/nrn2194

          35. Gu, Y., Oyama, F. & Ihara, Y. Tau is widely expressed in rat tissues. J. Neurochem. 67, 1235–1244 (2002). doi:10.1046/j.1471-4159.1996.67031235.x

          36. Trojanowski, J. Q., Schuck, T., Schmidt, M. L. & Lee, V. M. Distribution of tau proteins in the normal human central and peripheral nervous system. J Histochem Cytochem 37, 209–215 (1989).

          37. Morris, M., Maeda, S., Vossel, K. & Mucke, L. The many faces of tau. Neuron 70, 410–426 (2011).

          38. Mandelkow, E. M. et al. Structure, microtubule interactions, and phosphorylation of tau protein. Ann. N. Y. Acad. Sci. 777, 96–106 (1996).

          39. Noble, W., Hanger, D. P., Miller, C. C. J. & Lovestone, S. The importance of tau phosphorylation for neurodegenerative diseases. Front. Neurol. 4, 1–11 (2013).

          40. Gong, C.-X. & Iqbal, K. Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease. Curr. Med. Chem. 15, 2321–8 (2008).

          41. Martin, L., Latypova, X. & Terro, F. Post-translational modifications of tau protein: implications for Alzheimer’s disease. Neurochem. Int. 58, 458–471 (2011).

          42. Bloom, G. S. Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurol. 71, 505–8 (2014).

          43. Zempel, H., Thies, E., Mandelkow, E. & Mandelkow, E.-M. Abeta oligomers cause localized Ca(2+) elevation, missorting of endogenous tau into dendrites, tau phosphorylation, and destruction of microtubules and spines. J. Neurosci. 30, 11938–11950 (2010).

          44. Haass, C. & Mandelkow, E. Fyn-tau-amyloid: a toxic triad. Cell 142, 356–8 (2010).

          45. Ittner, L. M. et al. Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer’s disease mouse models. Cell 142, 387–397 (2010).

          46. Alberdi, E. et al. Amyloid beta oligomers induce Ca2+ dysregulation and neuronal death through activation of ionotropic glutamate receptors. Cell Calcium 47, 264–72 (2010).

          47. Bieschke, J. et al. Small-molecule conversion of toxic oligomers to nontoxic β-sheet-rich amyloid fibrils. Nat. Chem. Biol. 8, 93–101 (2012).

          48. Vingtdeux, V., Sergeant, N. & Buée, L. Potential contribution of exosomes to the prion-like propagation of lesions in Alzheimer’s disease. Front. Physiol. 3, 229 (2012).

          49. Frost, B. & Diamond, M. I. Prion-like mechanisms in neurodegenerative diseases. Nat. Rev. Neurosci. 11, 155–159 (2010).

          50. Murray, M. E. et al. Clinicopathologic and 11C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer’s disease spectrum. Brain 138, 1370–81 (2015).

          51. Forest, S. K., Acker, C. M., D’abramo, C. & Davies, P. Methods for measuring tau pathology in transgenic mouse models. J. Alzheimer’s Dis. 33, 463–471(2013). doi:10.3233/JAD-2012-121354

          52. Panza, F. et al. Tau aggregation inhibitors: the future of Alzheimer’s pharmacotherapy? Expert Opin. Pharmacother. 17, 457–461 (2016). doi:10.1517/14656566.2016.1146686

          53. Marsell, R. et al. GSK-3 inhibition by an orally active small molecule increases bone mass in rats. Bone 50, 619–627 (2012). doi:10.1016/j.bone.2011.11.007

          54. Ogawa, Y. et al. Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A. Nat. Commun. 1, 86 (2010). doi:10.1038/ncomms1090

          55. Conde, S., Pérez, D. I., Martínez, A., Perez, C. & Moreno, F. J. Thienyl and phenyl α-halomethyl ketones: new inhibitors of glycogen synthase kinase (GSK-3β) from a library of compound searching. J. Med. Chem. 46, 4631–3 (2003). doi:10.1021/jm034108b

          56. Abisambra, J. et al. Allosteric heat shock protein 70 inhibitors rapidly rescue synaptic plasticity deficits by reducing aberrant tau. Biol. Psychiatry 74: 367–374. (2013). doi:10.1016/j.biopsych.2013.02.027




          Get resources and offers direct to your inbox Sign up
          A-Z by research area
          • Cancer
          • Cardiovascular
          • Cell biology
          • Developmental biology
          • Epigenetics & Nuclear signaling
          • Immunology
          • Metabolism
          • Microbiology
          • Neuroscience
          • Signal transduction
          • Stem cells
          A-Z by product type
          • Primary antibodies
          • Secondary antibodies
          • Biochemicals
          • Isotype controls
          • Flow cytometry multi-color selector
          • Kits
          • Loading controls
          • Lysates
          • Peptides
          • Proteins
          • Slides
          • Tags and cell markers
          • Tools & Reagents
          Help & support
          • Support
          • Make an Inquiry
          • Protocols & troubleshooting
          • Placing an order
          • RabMAb products
          • Biochemical product FAQs
          • Training
          • Browse by Target
          Company
          • Corporate site
          • Investor relations
          • Company news
          • Careers
          • About us
          • Blog
          Events
          • Tradeshows
          • Conferences
          International websites
          • abcam.cn
          • abcam.co.jp

          Join with us

          • LinkedIn
          • facebook
          • Twitter
          • YouTube
          • Terms of sale
          • Website terms of use
          • Cookie policy
          • Privacy policy
          • Legal
          • Modern slavery statement
          © 1998-2023 Abcam plc. All rights reserved.