Different protein clumps indicate different types of Alzheimer's

US researchers investigating subtypes of Alzheimer’s disease have suggested that each subtype may differ in the structure of the protein clumps that aggregate in patients’ brains.

While the cause of Alzheimer’s is largely unknown, much attention has focused on clumps that are found in the brains of sufferers, called plaques, made up of a substance called amyloid-beta peptide. The development of amyloid-beta peptides into fine protein fibres called fibrils is a key feature of the disease, and it has been suggested that different fibril formations may be correlated with variations in disease subtypes.

To investigate this association, Robert Tycko and colleagues from the National Institutes of Health analysed amyloid-beta fibrils prepared from 37 brain tissue samples from 18 individuals. These included patients with either typical Alzheimer’s disease or two unusual subtypes — rapidly progressive Alzheimer's disease, in which neurodegeneration occurs within months, and posterior cortical atrophy Alzheimer’s disease, which is associated with disruption of visual processing.

Reporting in the journal Nature, the researchers found that a single specific fibril structure was dominant in samples from patients with either typical Alzheimer’s disease or the posterior cortical atrophy form. However, samples from patients with the rapidly progressive disease displayed a range of different fibril structures.

The findings support the theory that different clinical subtypes of Alzheimer’s might be defined by different amyloid-beta fibril structures and could be useful in developing new diagnostic tests for subtypes of the disease, the researchers said. However, Dr Bryce Vissel from the University of Technology Sydney and the Garvan Institute of Medical Research, who was not involved in the research, noted that the study does not prove that plaques or amyloids cause Alzheimer’s disease and that it is possible that amyloid is a marker of disease rather than the cause.