Conformation-Specific Aβ Antibodies – An Essential Tool for the Future of Alzheimer’s Disease Research


The complex pathology of Alzheimer’s disease may be known from the structural variation of beta amyloid (Aβ), which also emphasizes the need for conformation-specific antibodies.

Conformational Variation and Alzheimer’s Disease

Alzheimer’s disease is a complicated neurodegenerative condition showing symptoms that differ from patient to patient. The case for Aβ playing a vital role in disease pathology is compelling, yet its precise role remains unclear.

Alzheimer’s disease is characterized by the existence of plaques in the brain. The formation of insoluble fibrils due to clustering together of soluble oligomers formed by the spontaneous assembly of monomeric Aβ is the cause of formation of these plaques.

According to study results, both insoluble fibrils and soluble oligomers play a role in Alzheimer’s disease pathology, yet their precise role remains unclear.

There is no correlation between Aβ within the brain and the cognitive ability of patients, which is a major obstacle to understanding the role Aβ potentially plays in Alzheimer’s disease. For instance, some patients who have beta Aβ deposits do not show any symptoms of Alzheimer’s disease1–3.

The structural variations of Aβ may provide the answer to Alzheimer’s disease heterogeneity. Polymorphic Aβ oligomers can be formed by Aβ in a process called segmental polymorphism, where the segments forming beta sheets have different fibril structures4–6.

Hence, like prion diseases, the deposition of unique forms of structurally distinct Aβ occurs in different places and at different times within the brains of patients with Alzheimer’s disease, but which types of deposit are responsible for the cognitive symptoms of the disease is still under debate7.

The Need for Conformation-specific Antibodies

With increasing evidence to support the biomedical importance of Aβ structural variation, it is evident that conformation-specific Aβ imaging reagents is expected to play a key role in the future of Alzheimer’s research.

The clinical relevance of Aβ structural variation was highlighted in a recent study conducted in humans. Tissues collected from two Alzheimer’s disease patients having distinct clinical histories showed the presence of a predominant Aβ fibril structure in each patient; however, the dominant structure was different in each patient8.

Studies conducted in cultured cells and mice have also provided evidence in support of 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 brain9,10.

Moreover, the immune system convincingly reflects the complexity of Aβ structure, with study results showing that the antibodies generated in response to Aβ fibrils are diverse, showing their structural variation11,12.

Taking into account all evidence, it is very clear that it is not sufficient to use a single antibody to study or target all the potential pathological aggregates of Aβ that contribute to Alzheimer’s disease. This confirms that conformation-specific Aβ antibodies will serve as a vital tool for the future of Alzheimer’s disease research13–16.

Conformation-specific Amyloid Beta Antibodies

Abcam plc offers a wide range of antibodies to distinguish between the conformational variation in amyloid structures.

Amyloid beta (Aß) plaques show diverse conformations in Alzheimer's disease, causing structural variants with distinct pathologies. Abcam, in partnership with Professor Charles Glabe (UC Irvine), created rabbit monoclonal antibodies against Aß 1–42 fibrils that are capable of distinguishing between the conformational variation in amyloid structures.

  • Human Aß (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

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


Frontal cortex plaques

Layer V cortical and CA1 pyramidal neurons

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


Subset of frontal cortex plaques

Hippocampal plaques

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


Vascular amyloid deposits


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


Frontal cortex plaques


Anti-amyloid fibril antibody [mOC78] - conformation specific


Intracellular/nuclear, frontal cortex plaques

Layer V cortical neurons

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


Frontal cortex plaques

Layer V cortical neurons (intracellular deposits)

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


Frontal cortex plaques

Layer V cortical neurons (intracellular deposits)

Anti-amyloid fibril antibody [mOC116] - conformation specific


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


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About Abcam

Abcam is a global life sciences company providing highly validated antibodies and other binders and assays to the research and clinical communities to help advance the understanding of biology and causes of disease.

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Last updated: Feb 5, 2018 at 5:05 AM

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