Pathological differences in inherited versus sporadic Alzheimer's disease

The researchers are making new discoveries about the pathological changes in people who have inherited Alzheimer’s disease versus developing the disease sporadically. These findings could lead to new ways of preventing and treating the disease.

In a new paper published in Science, researchers detail new findings about senile plaques, which are made up of a peptide called Amyloid-β 42 (Aβ 42). The study shows for the first time that the structure of the Aβ 42 filaments is different in sporadic and inherited Alzheimer’s disease. Type I filaments were found mostly in the brains of individuals with sporadic Alzheimer’s disease and Type II filaments were found in individuals with familial Alzheimer’s disease or other neurodegenerative conditions.

“Although senile plaques have been known to be one of the main pathological changes in Alzheimer’s disease for over a century, their nature and composition has been gradually unraveled during the past four decades,” said the corresponding author of the paper.

Researchers looked at cryogenic electron microscopy maps and 3D structures of Aβ 42 from the brains of five patients with Alzheimer’s disease and from five patients with different neurodegenerative conditions. Patients had either sporadic Alzheimer’s disease or dominantly inherited Alzheimer’s disease with a mutation in the APP or PSEN1 genes.

“This new knowledge of the filament structures provides deeper insights into the disease process in Alzheimer’s and may lead to the development of compounds that can prevent the disease by inhibiting filament formation as well as new methods for brain imaging,” the author said. “This paper opens a new chapter for imaging and therapeutics.”