Site updated at Wednesday, 22 June 2016

Living with Dementia

New findings contradict dominant theory in Alzheimer’s disease

  • - Dementia News
  • Oct 28, 2011
  • Comments
  • Viewed: 1680
Tags: | alzheimer’s disease | beta-amyloid peptides |

For decades the amyloid hypothesis has dominated the research field in Alzheimer’s disease. The theory describes how an increase in secreted beta-amyloid peptides leads to the formation of plaques, toxic clusters of damaged proteins between cells, which eventually result in neurodegeneration. Scientists at Lund University, Sweden, have now presented a study that turns this premise on its head. The research group’s data offers an opposite hypothesis, suggesting that it is in fact the neurons’ inability to secrete beta-amyloid that is at the heart of pathogenesis in Alzheimer’s disease.

The study, published in the October issue of the Journal of Neuroscience, shows an increase in unwanted intracellular beta-amyloid occurring early on in Alzheimer’s disease. The accumulation of beta-amyloid inside the neuron is here shown to be caused by the loss of normal function to secrete beta-amyloid.

Contrary to the dominant theory, where aggregated extracellular beta-amyloid is considered the main culprit, the study instead demonstrates that reduced secretion of beta-amyloid signals the beginning of the disease.

The damage to the neuron, created by the aggregated toxic beta-amyloid inside the cell, is believed to be a prior step to the formation of plaques, the long-time hallmark biomarker of the disease.

Professor Gunnar Gouras, the senior researcher of the study, hopes that the surprising new findings can help push the research field in a new direction.

“The many investigators and pharmaceutical companies screening for compounds that reduce secreted beta-amyloid have it the wrong way around. The problem is rather the opposite, that it is not getting secreted. To find the root of the disease, we now need to focus on this critical intracellular pool of beta-amyloid.

“We are showing here that the increase of intracellular beta-amyloid is one of the earliest events occurring in Alzheimer’s disease, before the formation of plaques. Our experiments clearly show a decreased secretion of beta-amyloid in our primary neuron disease model. This is probably because the cell’s metabolism and secretion pathways are disrupted in some way, leading beta-amyloid to be accumulated inside the cell instead of being secreted naturally”, says Davide Tampellini, first author of the study.

The theory of early accumulation of beta-amyloid inside the cell offers an alternate explanation for the formation of plaques. When excess amounts of beta-amyloid start to build up inside the cell, it is also stored in synapses. When the synapses can no longer hold the increasing amounts of the toxic peptide the membrane breaks, releasing the waste into the extracellular space. The toxins released now create the seed for other amyloids to gather and start forming the plaques.
For more information:

Gunnar Gouras, Professor, Lund University, Sweden
Tel: +46 46 222 0309, email: .(JavaScript must be enabled to view this email address)

Davide Tampellini, Researcher
Tel: + 46 46 222 0310, mobile: +46 727 201092, email: .(JavaScript must be enabled to view this email address)

The publication: “Impaired β-Amyloid Secretion in Alzheimer’s Disease Pathogenesis” as published on the Journal of Neuroscience website.


Lund University

Post a comment [ + Comment here + ]

There are no comments for this entry yet. [ + Comment here + ]

Your details

* Required field

Please enter the word you see in the image below:

Comments are moderated by our editors, so there may be a delay between submission and publication of your comment. Offensive or abusive comments will not be published.

I have Alzheimer Disease

wernicke syndrome1 - amyloid-targeting treatment1 - mild alzheimer's stage1 - memory disorders2 - igf resistance1 - risk factors1 - beta-amyloid8 - fish oil supplements1 - early alzheimer's3 - melancholia2 - peripheral arterial disease1 - app3 - stress2 - dementia with lewy bodies3 - alzheimer's32 - lewy body disease1 - biomarkers in cerebrospinal fluid1 - dopamine-deficient worms1 - white matter hyperintensities1 - alzheimer's and parkinson's diseases1 - behavioral problems1 - beta-amyloid peptides1 - baroness thatcher1 - anoea1 - gammagard1 - treat alzheimer's1 - sodium benzoate1 - amyloid-β421 - degeneration theory1 - development of alzheimer's1 -