Seeing inside Alzheimer’s disease brain

Scientists investigating Alzheimer’s disease have determined the structure of molecules within a human brain for the very first time.

The study describes how scientists used cryo-electron tomography, guided by fluorescence microscopy, to explore deep inside an Alzheimer’s disease donor brain. This gave 3-dimensional maps in which they could observe proteins, the molecular building blocks of life a million-times smaller than a grain of rice, within the brain.

The study zoomed in on two proteins that cause dementia– ‘β-amyloid’, a protein that forms microscopic sticky plaques, and ‘tau’ – another protein that in Alzheimer’s disease forms abnormal filaments that grow inside cells and spread throughout the brain.

This study revealed the molecular structure of tau in tissue, how amyloids are arranged, and new molecular structures entangled within this pathology in the brain.

Dementia is the leading cause of death in the UK, with Alzheimer’s its most common form.

In Alzheimer’s disease, both β-amyloid plaques and abnormal tau filaments are thought to disrupt cellular communication, which leads to symptoms such as memory loss and confusion, and cell death.

Dr Rene Frank said: "This first glimpse of the structure of molecules inside the human brain offers further clues to what happens to proteins in Alzheimer’s disease but also sets out an experimental approach that can be applied to better understand a broad range of other devastating neurological diseases."

Read CryoET of β-amyloid and tau within postmortem Alzheimer’s disease brain on the Nature website

Read the full press release on the Faculty of Biological Sciences website.