Alzheimer's Disease (AD) is a degenerative disorder characterised by a progressive decline in cognitive function, memory loss, and behavioural changes. This article discusses the mechanisms of neuroinflammation, its implications for AD, and potential therapeutic breakthroughs targeting inflammation.

Alzheimer’s Disease is the most common form of dementia, affecting millions worldwide. Characterised by the accumulation of amyloid plaques and neurofibrillary tangles, the disease results in synaptic dysfunction and neurodegeneration.

However, accumulating evidence indicates that neuroinflammation plays a crucial role in the pathophysiology of AD. Neuroinflammation refers to the activation of the brain's immune response, including the activation of microglia and the release of pro-inflammatory cytokines, which can exacerbate neuronal injury [1].

Mechanisms of Neuroinflammation in Alzheimer’s Disease

Neuroinflammation in AD is mediated primarily by the activation of microglia, the resident immune cells of the CNS. Under normal circumstances, microglia maintain homeostasis; however, in response to amyloid-beta (Aβ) deposition, these cells become overactive, releasing inflammatory mediators such as cytokines, chemokines, and reactive oxygen species (ROS) [2]. This chronic inflammatory state contributes to neuronal cell death and synaptic dysfunction.

Role of Amyloid-Beta and Tau

1. Amyloid-Beta (Aβ): The aggregation of Aβ is the initiating event in AD pathology. Aβ oligomers are known to be highly neurotoxic and are potent stimuli for microglial activation. Microglia, in an attempt to clear Aβ, become hyperactivated and start a cycle of chronic inflammation [3].

2. Tau Pathology: Hyperphosphorylated tau protein leads to neurofibrillary tangles, another hallmark of AD. The presence of tau tangles can also elicit inflammatory responses, further contributing to synaptic dysfunction and cognitive decline [4].

Implications of Neuroinflammation for Alzheimer's Disease

The relationship between neuroinflammation and AD is complex. While microglial activation can serve protective roles, such as the clearance of toxic proteins, chronic inflammation is detrimental.

Breakthroughs in Therapeutic Approaches

Understanding neuroinflammation's role in AD has spurred research into targeted therapies:

1. Anti-inflammatory Drugs: Several studies have investigated the potential of non-steroidal anti-inflammatory drugs (NSAIDs) in reducing the risk of AD or slowing its progression. While some epidemiological studies suggest a protective effect, clinical trials have yielded mixed results [6].

2. Microglial Modulation: New approaches aimed at modulating microglial activity are being explored. Agents that promote an anti-inflammatory phenotype of microglia could provide therapeutic benefits by reducing neuroinflammation without compromising their protective functions [7].

3. Biomarker Development: Biomarkers for neuroinflammation, such as sTREM2 and YKL-40, have been identified and may help in assessing the inflammatory status in AD patients, guiding treatment decisions and improving early diagnosis [8].

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Partha Ghosh, BNYS, MD(YS), is a general physician and a medical writer from Siliguri, Darjeeling.