Alzheimer’s without symptoms? 12 rare cases may lead to a cure –

AMSTERDAM, Netherlands — Can someone have Alzheimer’s disease without ever experiencing a single symptom? According to a shocking new study, the answer appears to be yes. Researchers in the Netherlands have discovered several cases of Alzheimer’s where the patients never experienced any memory loss until the day they died.

So, what exactly made these individuals so resilient to the effects of Alzheimer’s? A team from the Netherlands Institute for Neuroscience says their examination of the brains of these patients could hold the answer to a new treatment for the disease.

Their work, published in the journal Acta Neuropathologica Communications, studied the brain tissue of more than 5,000 deceased brain donors stored in the Netherlands Brain Bank. These individuals chose to donate their brains to science after their deaths from a wide range of brain diseases. Researchers also had detailed medical records on each patient, as well as a full list of symptoms during their lifetime.

From that group of brain donors, study leader Luuk de Vries and the team discovered 12 extremely rare cases where a patient tested positive for Alzheimer’s disease but did not have any clinical symptoms or cognitive decline before death. The researchers are calling these special individuals “the resilient group.”

“Of all the donors we found 12, so it is quite rare. We think that genetics and lifestyle play an important role in resilience, but the exact mechanism is still unknown,” says de Vries in a media release.

Recent studies have documented how exercise, being cognitively active, and having a lot of social contact can delay the onset of Alzheimer’s disease. Moreover, having a cognitively stimulating job can also protect the brain from dementia later in life. Could these factors and the discovery of brains that resist the effects of Alzheimer’s lead to a cure?

“If we can find the molecular basis for resilience, then we have new starting points for the development of medication, which could activate processes related to resilience in Alzheimer’s patients,” de Vries continues.

Medicine, pills on top of brain MRI scans
Researchers in the Netherlands have discovered several cases of Alzheimer’s where the patients never experienced any memory loss until the day they died. (© Katsiaryna – stock.adobe.com)

So, what exactly was going on the brains of the resilient group? The team discovered several cellular factors that differ from the typical dementia patient.

“First of all, the astrocytes appeared to produce more of the antioxidant metallothionein. Astrocytes are like garbage collectors and provide a protective role for the brain,” de Vries explains.

The study author adds that astrocytes also frequently “ask for help” from microglia — immune cells in the brain and spinal cord. However, microglia can be very aggressive defenders of the central nervous system. This leads to harmful inflammation, which can exacerbate Alzheimer’s onset.

In the resilient group, the link between overactive microglia and Alzheimer’s was much less active. Additionally, the team found that the “unfolded protein response” — a reaction in brain cells that gets rid of misfolded toxic proteins — was functioning normally in the resilient group. In typical Alzheimer’s patients, this response doesn’t work properly, causing toxic proteins to build up in the brain and worsening cognitive decline.

“Finally, we found indicators that there may also be more mitochondria in the brain cells resilient individuals, which ensures better energy production,” de Vries adds.

So, what does all this mean for the future of Alzheimer’s research? Scientists are taking the first steps toward fully understanding how disease impacts the brain. However, this project used brain tissue from deceased donors. Future research will eventually need to focus on living patients to see if a treatment can effectively cure Alzheimer’s.

“It remains difficult to determine from human data which process initiates the disease process. You can only demonstrate this by changing something in cells or animal models and seeing what happens next. That is the first thing we have to do now,” de Vries concludes.

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