Calcium's impact on familial Alzheimer's disease clarified

Research by the Perelman School of Medicine (PSM) at the University of Pennsylvania has clarified the role of calcium in the development of familial Alzheimer's disease (FAD), which could influence future treatment for patients.

Previous studies, conducted in 2008 by the PSM, demonstrated that mutations in two proteins associated with FAD disrupt the flow of calcium ions within neurons. 

The two proteins, PS1 and PS2 (presenilin 1 and 2), interact with a calcium release channel in an intracellular compartment. According to the study, these mutant proteins result in an exaggerated calcium signaling in the cell, where normal proteins do not.

The same team, led by Dr J Kevin Foskett, chair of physiology and graduate student Dustin Shilling have found that, by suppressing the hyperactivity of the calcium channels, FAD-like symptoms could be alleviated in mice models of the disease. 

Speaking about the study, which is published in the latest edition of the Journal of Neuroscience, Dr Foskett said his team set out to find whether or not increased calcium signaling had an impact on FAD symptoms, such as dementia or cognitive deficits.

He added that, as a result of the study, it is clear that increased calcium signaling does have an influence on the presentation of symptoms in FAD patients.

Currently incurable, the available therapies for Alzheimer's sufferers include prescribing drugs that can either treat cognitive loss and dementia or attempt to address the pathology of Alzheimer's, but these are experimental.

It is hoped that this research could lead to further investigations into the possibility of developing methods based on modulating calcium signaling, according to Dr Foskett.

The 'calcium dysregulation' hypothesis for inherited, early-onset FAD has been suggested by Dr Foskett's previous research but the new study provides further clarification on the matter.

Based on American statistics, around five per cent of all Alzheimer's patients have FAD, but it is unclear whether this research could help the most common form of the disease.

"There has been an assumption that FAD is simply Alzheimer's disease (AD) with an earlier, more aggressive onset," added Dr Foskett. 

"What's important, in my opinion, is to recognise that AD could be a spectrum of diseases that result in common end-stage pathologies."