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Amyloid plaques - protein deposits in the brain & their role in Alzheimer's disease

Amyloid plaques are protein deposits in the brain and are considered to be the main feature of Alzheimer's disease. Find out all about their development, diagnostic methods and new therapeutic approaches here.

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Things worth knowing about "Amyloid plaques"

Amyloid plaques are protein deposits in the brain and are considered to be the main feature of Alzheimer's disease. Find out all about their development, diagnostic methods and new therapeutic approaches here.

Amyloid plaques are insoluble deposits of a misfolded protein fragment called amyloid-β (Aβ) in the brain. They are considered a central pathological feature of Alzheimer's disease and are suspected of contributing significantly to the destruction of nerve cells and synapses. The formation of these plaques often begins many years before the first symptoms appear and plays a key role in neurodegenerative development.

Development

Amyloid-β is formed by the cleavage of the amyloid precursor protein (APP) into smaller fragments. In healthy people, Aβ is normally broken down and removed from the brain. However, if overproduction or impaired degradation occurs, the Aβ fragments accumulate and form extracellular plaques between the nerve cells.

These deposits activate inflammatory processes in the brain, promote oxidative stress and impair signal transmission in the synaptic cleft, which leads to the death of nerve cells in the long term.

Importance in Alzheimer's

Amyloid plaques are one of the two main histopathological features of Alzheimer's dementia - alongside the tau protein changes inside the cell. The so-called amyloid cascade hypothesis assumes that Aβ deposits are the first step in the disease process, which leads downstream to tau pathology, neuroinflammation and neuronal degeneration.

However, the connection is not fully understood, as amyloid plaques are also detectable in some cognitively healthy older people. This points to a complex multifactorial pathogenesis.

Detection of amyloid plaques

Amyloid plaques can be detected diagnostically using various methods:

  • Cerebrospinal fluid analysis: Low Aβ42 level in the cerebrospinal fluid is considered an indication of plaque formation

  • PET imaging: Special radiotracers (e.g. florbetapir) enable direct detection in the living brain

  • Post-mortem tissue analysis: Histological detection in the brain

Therapeutic approaches

The targeted influencing of amyloid formation is the focus of new Alzheimer's therapies:

  • Monoclonal antibodies (e.g. lecanemab, aducanumab) bind to amyloid peptides and promote their degradation

  • BACE inhibitors are designed to reduce the production of amyloid-β (with limited success so far)

  • Lifestyle interventions such as exercise, healthy eating and cognitive activity can have a preventative effect

Amyloid plaques are not the sole cause, but they are an important diagnostic and therapeutic starting point in Alzheimer's disease

.

Literature references:

  • Selkoe, D. J. & Hardy, J. (2016). "The amyloid hypothesis of Alzheimer's disease at 25 years."" EMBO Molecular Medicine.

  • Jack, C. R. et al. (2018). ""NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease." Alzheimer's & Dementia.

  • German Alzheimer's Society (2023). "Biomarkers in Alzheimer's diagnostics.""

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