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This Could Help Detect One-Third of Future Alzheimer’s Cases

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A new study reveals what happens during the earliest stages of Alzheimer’s disease and subtle signs that may appear much before the first plaques or cognitive deficits become detectable

Alzheimer’s disease does not suddenly manifest when symptoms become apparent. Instead, a prolonged period of silence ensues, spanning several decades, during which the underlying pathology of the disease progresses unnoticed. But what exactly unfolds during this elusive phase?

It is believed that genetic factors contribute approximately two-thirds to the risk of Alzheimer’s disease (AD), leaving a third of the risk attributed to environmental and lifestyle elements. This proportion presents potential opportunities for lifestyle-based interventions that may prevent or slow down the physiological deteriorations associated with AD.

A recent study, using a mouse model for AD, has explored the impact of enriched environments on the progression and manifestation of AD symptoms.

This research has been published in Biological Psychiatry.

Dr. Gerd Kempermann, from the German Center for Neurodegenerative Diseases in Dresden, Germany, the study’s lead author, underscored the significance of investigating the initial stages of the disease, as this is the period when interventions have the potential to yield the most substantial results.

“AD[Alzheimer’s disease] does not start when the symptoms become obvious,” points out the lead author.

“There is a decades-long silent period, during which the pathology progresses undetected. Clinicians and researchers have become increasingly interested in what happens during this phase.”

Dr. Kempermann and his team focused on understanding the initial stages of Alzheimer’s disease (AD) by employing a specially engineered mouse model that mirrors this pre-symptomatic phase.

This mouse model is characterized by numerous genetic alterations in the gene responsible for the production of the amyloid precursor protein (App) – alterations that are also known to occur in human AD.

This specific strain of mice, known as AppNL-F, exhibits the formation of harmful amyloid-beta accumulations, commonly referred to as plaques, by the time they reach half a year of age. Furthermore, signs of cognitive decline become apparent when these mice reach the age of 18 months.

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But, the researchers found “that there are already subtle but important behavioral changes long before the first plaques appear, and the cognitive deficits become detectable.”

The rodents were accommodated in a complex habitat comprising 60 linked enclosures, starting at 6 weeks and lasting till their 23rd week of age. Subsequently, they were transferred to more conventional settings after a period of 4 months. Residing in this complex environment enhanced numerous metabolic indices, all of which are recognized as potential risk determinants for Alzheimer’s disease.

Dr. Kempermann shed light on the fact that mice in their AD model study exhibited a decrease in diverse behaviors, resulting in increased rigidity and conformity.

This indicates that the essence of individualization, which largely hinges on personal behavior and brain adaptability, was undermined. It’s clear that these mice exhibited symptoms of behavioral impairment early in the disease progression. They didn’t react to environmental stimuli as expected.

“This finding is important, because it will help us to understand how we can best tailor preventive measures during the pre-clinical phase. It also underscores that prevention has to start early,” adds the author.

The study team also studied signs of new nerve cell development in the mice. Surprisingly, the AppNL-F mice exhibited a greater frequency of nerve cell creation compared to the control mice. This is believed to be a failed attempt at self-regulation and ironically, it appears to be more damaging than beneficial. However, this overactive compensatory response was effectively regulated when the mice were exposed to an enriched environment.

“This novel study suggests that environmental enrichment may reduce the early accumulation of amyloid plaques in a mouse model of AD,” comments John Krystal, MD, Editor of Biological Psychiatry.

“This insight may suggest a strategy for delaying the development of symptoms associated with this disorder.”

Image Credit: Getty

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