Beyond Neurons: New Hopes in the Fight Against Alzheimer's Disease

Studies Reveals Microglia's Role in Alzheimer's Progression, and the Potential of Shp2

Recent studies have shed light on the critical role of microglia in the progression of Alzheimer’s disease, uncovering how these specialized immune cells in the brain contribute to neurodegeneration. Microglia, which act as the brain’s first line of defense, are involved in clearing cellular debris and maintaining neural health. However, in Alzheimer’s, they can become overactive, leading to chronic inflammation and damage to surrounding neurons. 

Alzheimer's research has mainly targeted neurons, as beta-amyloid plaques in the synaptic spaces disrupt their communication, contributing to cognitive decline and Alzheimer's symptoms.

Researchers have also identified Shp2, a signaling protein, as a potential therapeutic target. Modulating Shp2 activity could help regulate microglial behavior, reducing harmful inflammation while preserving their protective functions. These findings open promising avenues for developing treatments aimed at slowing or halting the progression of Alzheimer’s disease.

New research in 2025 confirms that microglia—once overlooked—are central to Alzheimer’s progression and may hold the key to future treatments. Scientists now view these immune cells as both contributors to disease and potential therapeutic allies.

Microglia: From Bystanders to Key Players

Traditionally, Alzheimer’s research focused on neurons and beta-amyloid plaques. But 2025 studies have revealed that microglia—the brain’s resident immune cells—actively shape disease progression. Their behavior influences inflammation, plaque accumulation, and even astrocyte reactivity.

• Microglia modulate astrocyte reactivity, which is linked to beta-amyloid toxicity. When microglia are reactive, astrocytes show heightened responses that may worsen neurodegeneration.
• A newly identified protective subtype of microglia appears to reduce inflammation and slow disease spread. These cells help preserve memory and brain function.
• Lipid droplets in microglia, once ignored, are now seen as a hallmark of Alzheimer’s. They may connect APOE4 gene variants to nerve-cell death and offer a unified theory of disease progression.

New research confirms Shp2’s pivotal role in Alzheimer’s and Parkinson’s, offering fresh therapeutic targets and personalized treatment potential.

Shp2: A Master Regulator in Brain Health

Shp2, a protein encoded by the PTPN11 gene, acts like a cellular traffic controller—regulating signals that affect brain cell survival, communication, and repair. In 2025, studies published in Nature Translational Psychiatry and other journals have revealed that Shp2 is deeply involved in the pathology of Alzheimer’s and Parkinson’s diseases.

In Alzheimer’s Disease:

• Shp2 interacts with Tau and Aβ proteins, influencing their accumulation and toxicity.
• It modulates tyrosine kinase-dependent signaling, which affects synaptic function and neuroinflammation.
• Dysregulated Shp2 activity contributes to neuronal stress and degeneration, making it a promising therapeutic target.

In Parkinson’s Disease:

1. Shp2 regulates Parkin, a protein essential for clearing cellular waste and damaged mitochondria.
2.  Altered Shp2 signaling may impair autophagy and proteostasis, accelerating neurodegeneration.