Exploring the Alzheimer’s brain

For the first time, scientists studying Alzheimer’s disease have mapped the structure of molecules in a human brain. Published in Nature, the study used cryo-electron tomography, guided by fluorescence microscopy, to explore inside an Alzheimer’s donor brain. This provided 3D maps to observe proteins, the tiny building blocks of life, within the brain, a million times smaller than a grain of rice.

The study focused on two proteins linked to dementia: ‘β-amyloid,’ which forms sticky plaques, and ‘tau,’ which forms abnormal filaments in Alzheimer’s disease. It revealed the molecular structures of tau in brain tissue and how amyloids are arranged, uncovering new molecular structures within this brain pathology. Dementia, especially Alzheimer’s disease, is the UK’s leading cause of death.

In Alzheimer’s disease, β-amyloid plaques and abnormal tau filaments disrupt cell communication, causing symptoms like memory loss, confusion, and cell death.

This new insight into brain molecules provides clues about Alzheimer’s disease. It suggests an experimental method for studying other neurological diseases.

Dr. Rene Frank, the lead author and associate professor at the School of Biomedical Sciences, highlighted how researchers have traditionally studied isolated proteins in test tubes for decades despite knowing that biological functions often involve many proteins working together like an orchestra.

This University of Leeds study, in collaboration with scientists from Amsterdam UMC, Zeiss Microscopy, and the University of Cambridge, is part of a new approach to structural biology.

Researchers are now studying proteins directly within cells and tissues, their natural environment, to understand how proteins interact and influence each other, especially in diseased human cells and tissues. This method aims to identify new targets for advanced therapies and diagnostics by observing protein interactions within tissues.

Journal reference:

1. Gilbert, M.A.G., Fatima, N., Jenkins, J., et al. CryoET of β-amyloid and tau within postmortem Alzheimer’s disease brain. Nature. DOI: 10.1038/s41586-024-07680-x.