Hide menu

Poor ”waste disposal” could explain Alzheimer’s

Poor waste disposal in the brain’s neurons may lie behind Alzheimer’s disease. Instead of being broken down, harmful protein waste accumulates, causing cell death. Reinforcing the waste management system is a possible strategy for halting the progress of the disease.

Two now well-known proteins – beta amyloid and tau – are at the centre of all research into Alzheimer’s. Large quantities of these proteins are found in the neurons of deceased patients during autopsy. Studies at Linköping University (LiU) now show that two “refuse collection” systems in the cells play a key role in the development of the disease.

Lotta Agholme, doktorand i geriatrik

“Both these systems – the proteasomal and the lysosomal – seem to be damaged in Alzheimer’s patients,” explains Lotta Agholme (pictured), graduate student in geriatrics, who is now preparing her doctoral thesis.

The proteasome is a “barrel whose job is to capture used proteins and chew them into bits. The lysosome is a bubble with acid enzymes that dissolve things like damaged proteins. A healthy brain functions as a loop where different constituents are continuously broken down and reused.

In a cell model, the Linköping researchers are studying what happens when the two systems are put out of action. When they added a substance that inhibits the functions of proteasomes, it led to several of the familiar changes of Alzheimer’s: accumulation of the protein beta amyloid, harmful changes in the tau protein and impaired transport along the nerve fibres.

In the laboratory these toxic changes took place over several days, a process that could take several years in the human brain. The research team also illustrated, for the first time, how the toxic protein may be transmitted from one neuron to the next via the fibres that connect cells to each other. In this way the “infection” is spread through the brain.

One possible course of events is that the neurons that receive too much beta-amyloid, for example because the refuse disposal is not working, try to get rid of it by passing it on to a neighbouring cell. So far the search for a treatment for Alzheimer's has predominately focused on preventing the creation of beta-amyloid.

“It would be interesting to look at whether the improved function of proteasomes and lysosomes might provide an alternative strategy,” says Agholme.

The involvement of clearance pathways and neuron-to-neuron transmission in Alzheimer’s disease, Linköping University Medical Dissertations No 1317. Defence of the thesis took place on Friday, October 5th, 2012 at 13:00 in Nils-Holger-salen, Campus US, Linköping. The examiner was Gunnar Gouras of Lund University.

Lotta Agholme +46 101 031 500, +46 705 533 308 

Text: Åke Hjelm


Page manager: johan.jager@liu.se
Last updated: 2012-12-10