Scientists discover simple root cause of Alzheimer’s disease

Study identifies potential drug targets to reverse brain pH imbalance.

Brain pH linked to Alzheimer’s

Scientists have discovered new evidence that one root cause of Alzheimer’s disease may be a simple imbalance in pH chemistry in the brain.

Brain cells called astrocytes work to clear so-called amyloid beta proteins from the spaces between neurons. But if the clearing process goes awry, amyloid proteins pile up, leading to the characteristic amyloid plaques and nerve cell degeneration that are the hallmarks of Alzheimer’s

In a new study from John Hopkins Medicine, mice with an Alzheimer’s gene were given histone deacetylase (HDAC) inhibitors. The experiment successfully reversed the pH problem and improved the capacity for amyloid beta clearance.

The scientists say they are planning additional experiments to see if HDAC inhibitors have a similar effect in lab-grown astrocytes from Alzheimer’s patients.

However, the scientists caution that even before those experiments can happen, far more research is needed to verify and explain the precise relationship between amyloid proteins and Alzheimer’s disease, which affects an estimated 50 million people worldwide. To date, there is no cure and no drugs that can predictably or demonstrably prevent or reverse Alzheimer’s disease symptoms.

“By the time Alzheimer’s disease is diagnosed, most of the neurological damage is done, and it’s likely too late to reverse the disease’s progression,” says Professor of Physiology at the Johns Hopkins University, Rajini Rao.

“That’s why we need to focus on the earliest pathological symptoms or markers of Alzheimer’s disease, and we know that the biology and chemistry of endosomes is an important factor long before cognitive decline sets in.”

Nearly 20 years ago, scientists at Johns Hopkins and New York University discovered that endosomes, compartments that ferry molecules within cells, are larger and more abundant in the brains of people destined to develop Alzheimer’s disease. This hinted at an underlying problem that could lead to an accumulation of amyloid protein in spaces around neurons, says Prof. Rao.

To shuttle their cargo from place to place, endosomes use chaperones – proteins that bind to specific cargo and bring them back and forth from the cell’s surface.

Whether and how well this binding occurs depends on the proper pH level inside the endosome, a delicate balance of acidity and alkalinity, that makes endosomes float to the surface and slip back down into the cell.

Embedded in the endosome membrane are proteins that shuttle charged hydrogen atoms, known as protons, in and out of endosomes. The amount of protons inside the endosome determines its pH.

When fluids in the endosome become too acidic, the cargo is trapped within the endosome deep inside the cell. When the endosome contents are more alkaline, the cargo lingers at the cell’s surface for too long.

Do you think this discovery could lead to earlier detection of Alzheimer’s disease?

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    COMMENTS

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    jackie
    7th Aug 2018
    11:03am
    Maybe an alkaline diet could help.
    Andy Leucite
    7th Aug 2018
    11:06am
    There are all kinds of exciting research projects being conducted on Alzheimer's disease, and the pH angle sounds like another promising direction. There is no doubt that the ability to detect well ahead of time the tendency to develop the disease is a goal that is important to many of the other bits of understanding about what is going on in the brain that might lead to the awful condition, amyloid plaque build up is one such happening that seems to be a key part of Alzheimer's developing eventually. There is a lot of effort going into the early detection business, for example trying to find possible biomarkers in the blood or urine which could indicate well ahead of time that some kind of treatment needs to be applied long before damage is already done. I am a volunteer in one of these research programs being conducted to look for some harbinger. This one is the AIBL study, and is being done at the Mental Health Institute in Parkville, Vic. My participation just involves giving blood and urine samples from time to time, and doing a few cognitive function tests. Good fun, but no other rewards, other than perhaps a warm inner glow - it's just a way of giving something back to the world. Those of you who are retired and would like to get out and about and talk to some inspiring people doing inspiring work, think seriously about volunteering in one of these projects. Perhaps Your Life Choices could write an article one day on becoming a volunteer. There are many other types of medical research projects that need you. I have been in another one that has been looking for biomarkers that might give early warning of a future tendency to have a nasty cardiovascular event - this could help prevent heart attacks, strokes etc. I am already too old (75) to benefit from any success in these sorts of programs, but knowing that perhaps some in the following generations might benefit contributes to the warm inner glow!!
    Jenny
    7th Aug 2018
    12:41pm
    I have participated in two research programs so far, both involving donations of blood and urine. I agree, it does give a feeling of satisfaction to know one is making a contribution however small.
    Mary
    7th Aug 2018
    11:10am
    I agree, Jackie. An alkaline diet is important for the whole body. An acid diet causes osteoporosis (which I have). Cancer has trouble surviving in an alkaline environment. So why wouldn't it damage the brain also?
    Alula
    7th Aug 2018
    1:06pm
    It's been shown that the alkaline diet is good for us, but not for the reasons we may think.
    Check out ABC health for this article: Alkaline diets: Good for your health or just another fad? (Sorry it's not a link.)
    "...shelling out for specialty waters, supplements and programs to alkalise your body is unlikely to help you avoid complex health conditions, because diet is not going to change the pH of your blood."
    musicveg
    17th Sep 2018
    2:03am
    Just eating more vegies and fruit, less processed food, less or no meat,eggs and dairy, will give you a better chance at having an alkaline diet. Best choice to prevent disease is wholefood, low fat, plant based diet.
    Jennie
    7th Aug 2018
    3:26pm
    "Whether and how well this binding occurs depends on the proper pH level inside the endosome, a delicate balance of acidity and alkalinity, that makes endosomes float to the surface and slip back down into the cell."
    "When fluids in the endosome become too acidic, the cargo is trapped within the endosome deep inside the cell. When the endosome contents are more alkaline, the cargo lingers at the cell’s surface for too long."

    So what pH is needed where? Slightly acidic? Slightly alkaline? It almost sounds as if it should be pH7 which is neutral.
    Charlie
    7th Aug 2018
    4:02pm
    Scientists discover root cause of Alzheimers, but they forgot............to explain it in english


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