Researchers unlock specific mechanisms behind Aβ-induced cytoxicity in Alzheimer's disease

Alzheimer's disease is a progressive neurodegenerative disorder that leads to dementia via advanced neuronal dysfunction and death. A person with Alzheimer's disease suffers loss of control over thought, memory and language abilities. Additionally, the disease takes an emotional, social and economic toll on family members of individuals living with the disease. Alzheimer's disease is also a burden for health care system in the U.S., with as many as 5 million Americans living with the disease in 2013, according to the U.S. Centers for Disease Control and Prevention, and that number is expected to continue rising.

Currently, the predominant theory behind Alzheimer's disease is the "amyloid hypothesis," which states that abnormally increased levels of amyloid beta (Aβ) peptides outside of brain cells produce a variety of low molecular weight Aβ aggregates that are toxic to the nervous system. These Aβ aggregates interact directly with target cells and lead to cell death.

During the Biophysical Society's 61st Annual Meeting, being held Feb. 11-15, 2017, in New Orleans, Louisiana, Antonio De Maio, a professor of surgery and neuroscience at the University of California, San Diego (UCSD), will present his work hunting for the specific mechanisms behind Aβ-induced toxicity to cells, or cytoxicity.

Cells exposed to stressful conditions respond by expressing heat shock proteins (hsps), whose job is to preserve cell viability. Hsp70, in particular, is a molecular chaperone that plays a major role in protein folding and the solubilization of misfolded, aggregated polypeptide proteins inside cells.

The researchers were interested in Hsp70 because, according to De Maio, it has also been found outside of cells, potentially coexisting with Aβ peptides.
His team observed that HsP70 did, in fact, reduce oligomerization of Aβ peptides.

Significantly, the researchers further inferred that the reduced oligomerization of Aβ, where individual monomer molecules join to form a longer oligomer, might result in lower cellular toxicity, perhaps by blocking the assembly of Aβ ion channels. And in fact this is what they found, demonstrating a substantial reduction -- approximately 70 percent -- of Aβ peptide's toxicity upon co-exposure to Hsp70.

"Based upon these observations, we predicted that inducing the extracellular release of Hsp70 might have a beneficial effect on Alzheimer's disease," said De Maio. "But it should be taken into consideration that we don't know any potential long-term side effects of extracellular Hsp70 for human health."

While extremely promising at this stage, "more investigations of the interface between Hsp70 and Aβ peptides are necessary for any further developments," De Maio said.


  1. Gary Chandler Gary Chandler United States says:

    Neurodegenerative disease is the fastest-growing cause of death in the world. The spike in autism is identical in timing and severity. It's time to expand the conversation immediately. Misdiagnosis, suppression of diagnoses, misinformation and mismanagement are contributing to the epidemic. Alzheimer's is part of a spectrum disease called transmissible spongiform encephalopathy (prion disease). The operative word is transmissible. The spectrum also includes the very aggressive, very deadly and very transmissible form known as Creutzfeldt-Jakob disease. In fact, it’s estimated that at least 25% of those diagnosed with Alzheimer’s disease actually have CJD, which is further up the spectrum. As such, spouses of those with "Alzheimer's" disease, for example, are 600% more likely to contract the infectious disease. Infectious waste has become a major part of the equation. It's now spreading to wildlife, livestock and back to humans because of sewage mismanagement.

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