New research sheds light on Alzheimer’s disease protection

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Alzheimer’s disease is a significant health concern worldwide.

It is a type of dementia that gradually worsens over time, affecting memory, thinking skills, and the ability to carry out simple tasks.

Despite numerous studies and advancements, scientists are still trying to unravel the mysteries of this disease.

A Unique Case Sparks Fresh Insights

Sometimes, a single patient can offer new insights and answers about a disease.

A fascinating case has come to light, as reported in Nature Medicine, about a patient who had a genetic predisposition to develop Alzheimer’s disease early but remained mentally sharp until his late 60s.

The international team leading the research included experts from Massachusetts General Hospital (MGH), Mass Eye and Ear, the University of Antioquia in Colombia, Children’s Hospital Los Angeles, and University Medical Center Hamburg-Eppendorf in Germany.

They worked together to understand why this patient was an exception to the norm.

A Protective Genetic Variant

The team found a new genetic variant that seems to offer protection against Alzheimer’s disease.

This variant was found in a different gene than a similar case reported in 2019, but both seem to influence the same disease pathway.

The Paisa Mutation

The patient belonged to a family known for carrying a genetic variant called the “Paisa” mutation (Presenilin-1 E280A).

Usually, carriers of this variant develop mild cognitive impairment around age 44, dementia around age 49, and typically die from complications of dementia in their 60s.

This man, however, remained mentally sharp until he was 67, developed mild dementia at 72, and died at 74—much later than the typical progression for people with the Paisa mutation.

The Power of Individual Cases

Such extraordinary cases can significantly advance our understanding of Alzheimer’s disease and pave the way for new discoveries.

“The insights we are gaining from this second case may guide us on where in the brain we need to look to delay and stop disease progression,” said co-senior author Yakeel T. Quiroz, Ph.D., a clinical neuropsychologist and neuroimaging researcher at Massachusetts General Hospital.

The Reelin-COLBOS Variant

The protective genetic variant, named Reelin-COLBOS, was discovered through extensive genetic and molecular analyses. Reelin is a protein with a critical role in brain cell development and function.

It competes with APOE, another protein, to bind to similar cellular receptors.

When Reelin binds the receptor, it decreases the phosphorylation of tau, a protein known to form pathological tangles in brains with Alzheimer’s disease.

Focusing on the Entorhinal Cortex

Interestingly, the patient’s brain scans revealed that his entorhinal cortex, a region crucial for memory and learning, had very limited tau pathology.

This finding suggests that targeting key brain structures such as the entorhinal cortex could be a successful strategy against dementia.

Potential New Treatments

The findings from this research could point to new treatment avenues. Current Alzheimer’s disease treatments mostly focus on reducing amyloid plaque buildup.

However, the two patients with the protective variant had high levels of amyloid in their brains but were still protected.

The Road Ahead

While other factors might have contributed to the patient’s resilience against Alzheimer’s symptoms, experimental evidence strongly suggests the protective role of the Reelin-CBOS variant.

The team of researchers plans to continue their work, aiming to identify more such extraordinary cases from these Colombian families.

They believe that each unique case holds valuable lessons that can further our understanding of Alzheimer’s disease.

If you care about brain health, please read studies about vitamin D deficiency linked to Alzheimer’s and vascular dementia, and higher magnesium intake could help benefit brain health.

For more information about brain health, please see recent studies about antioxidants that could help reduce dementia risk, and coconut oil could help improve cognitive function in Alzheimer’s.

The study was published in Nature Medicine.

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