Alzheimer’s disease attacks the brain in two separate phases

On the perpetual quest to understand Alzheimer’s, an unexpected breakthrough has been made, shedding light on ithe elusive nature and phases of the disease.

New research has led to the intriguing hypothesis that Alzheimer’s disease may wreak havoc on the brain in two distinct and destructive phases, fundamentally altering our understanding of its progression.

This fascinating and potentially game-changing discovery was funded by the National Institutes of Health (NIH) and made possible through advanced brain mapping tools.

The research could revolutionize the way we perceive, diagnose, and ultimately treat Alzheimer’s disease, offering renewed hope for patients and caregivers alike.

Alzheimer’s first phase

The preliminary phase of Alzheimer’s disease sneaks in subtly. Before anyone detects memory lapses or disorientation, this quiet intruder is already at work, silently assaulting a select few cell types.

This silent destruction is the prelude, setting the stage for more noticeable and widespread damage.

“One of the challenges to diagnosing and treating Alzheimer’s is that much of the damage to the brain happens well before symptoms occur,” noted Dr. Richard J. Hodes, director of NIH National Institute on Aging.

“The ability to detect these early changes means that, for the first time, we can see what is happening to a person’s brain during the earliest periods of the disease.”

It is this early detection that provides a glimmer of hope. The ability to glimpse into the initial stages of the disease provides a time window of potential intervention. It empowers scientists to comprehend and, possibly, influence the progression of this devastating disorder.

Second phase of Alzheimer’s

The second phase is where the disease truly flexes its muscle. This phase encapsulates most of the changes traditionally seen during the progression of Alzheimer’s disease.

It is during the second phase that symptoms become evident, and the brain experiences rapid accumulation of Alzheimer’s hallmarks – plaques and tangles.

In this study, researchers analyzed 84 brains in fine detail, focusing on the middle temporal gyrus – a region responsible for language, memory, and vision. This area is highly vulnerable to Alzheimer’s disease.

By comparing data from regular donors with data from Alzheimer’s patients, an enlightening genetic and cellular timeline of the disease emerged.

Targets of Alzheimer’s phases

Alzheimer’s transformation of the brain was found to occur in two “epochs.” The first phase, gradual and quiet, includes the slow accumulation of plaques, activation of the brain’s immune system, and damage to cellular insulation which aids neuron signal transmission.

Most surprising was the discovery that the disease targets a particular kind of cells called SST inhibitory neurons during this phase, contradicting the traditional belief that Alzheimer’s primarily damages excitatory neurons.

This finding was unexpected because inhibitory neurons are responsible for sending calming signals to other cells, while excitatory neurons send activating signals.

The researchers hypothesize that the loss of these calming SST inhibitory neurons may set off a domino effect leading to disorders in the brain’s neural circuitry, igniting the onset of the disease.

Potential resilience against Alzheimer’s

Parallel to this study, another NIH-funded research project at MIT suggested there is a potential protective factor.

A gene named REELIN, found in star-shaped brain cells called astrocytes, may offer some resilience against Alzheimer’s disease. Astrocytes might be capable of resisting the harm inflicted by the disease.

These findings resulted from studying over 3.4 million brain cells from donors at various stages of Alzheimer’s disease, utilizing tools developed by the NIH’s BRAIN Initiative – Cell Census Network (BICCN).

The tissue samples were obtained from the Adult Changes in Thought study and the University of Washington Alzheimer’s Disease Research Center.

Significance of the study

“This research demonstrates how powerful new technologies provided by the NIH’s BRAIN Initiative are changing the way we understand diseases like Alzheimer’s,” stated Dr. John Ngai, director of The BRAIN Initiative.

As the fight against Alzheimer’s phases and other dementias continues, the findings offer a new lens to look at the disease, potentially guiding the development of targeted diagnostic tools and treatments for specific stages of Alzheimer’s.

The study is published in the journal Nature Neuroscience.

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