Introduction
Alzheimer’s disease is a progressive neurodegenerative disorder that primarily affects the elderly. It leads to memory loss, cognitive decline, and behavioral changes. It is the most common cause of dementia. The exact cause is not fully understood, but it involves complex interactions of genetic, environmental, and lifestyle factors. Two hallmark features of Alzheimer’s disease are the accumulation of amyloid beta (Aβ) plaques and the formation of tau protein tangles.
Pathophysiology of Alzheimer’s Disease
The pathophysiology of Alzheimer’s disease is characterized by several cellular and molecular changes that impair neuronal function and communication.
1. Amyloid Beta Plaques
- Abnormal accumulation of amyloid beta peptides in the brain is one of the earliest events in Alzheimer’s pathology.
- Amyloid beta is derived from the cleavage of amyloid precursor protein (APP) by beta and gamma secretases.
- When not cleared efficiently, Aβ aggregates into insoluble plaques that deposit in the extracellular space.
Consequences of Amyloid Beta Accumulation:
- Disrupts communication between neurons
- Triggers an inflammatory response from glial cells
- Promotes oxidative stress and neuronal toxicity
2. Tau Protein and Neurofibrillary Tangles
- Tau is a protein associated with microtubules that help in transporting nutrients and signals inside neurons.
- In Alzheimer’s, tau protein becomes abnormally phosphorylated and detaches from microtubules.
- These hyperphosphorylated tau proteins aggregate and form twisted structures called neurofibrillary tangles (NFTs).
Consequences of Tau Pathology:
- Disrupts the internal transport system of neurons
- Leads to cell death and loss of brain tissue
- Correlates with the severity of cognitive decline
3. Synaptic and Neuronal Loss
The buildup of plaques and tangles leads to widespread synaptic dysfunction. Neurons begin to die, particularly in the hippocampus (responsible for memory) and the cerebral cortex (involved in thinking and planning).
4. Inflammation and Oxidative Stress
Microglial activation and release of pro-inflammatory cytokines worsen the neurodegenerative process. Reactive oxygen species (ROS) damage lipids, proteins, and DNA in neurons.
5. Brain Atrophy
Over time, the brain shrinks due to the loss of neurons and connections. This results in cognitive impairment and behavioral changes seen in Alzheimer’s patients.
Stages of Alzheimer’s Disease
- Preclinical: No symptoms but brain changes have started.
- Mild Cognitive Impairment (MCI): Slight memory and thinking problems.
- Mild to Moderate Stage: Noticeable memory loss, confusion, and difficulty performing daily tasks.
- Severe Stage: Complete dependence on others, loss of bodily functions, and inability to communicate.
Role of Amyloid Beta and Tau Protein
Amyloid Beta Plaques:
- Act as a trigger for the neurodegenerative cascade
- May disrupt synaptic function and initiate inflammatory processes
Tau Protein:
- Directly linked with neuron death and brain shrinkage
- Severity of symptoms correlates more with tau tangle density than with amyloid plaque load
Conclusion
Alzheimer’s disease is a complex disorder involving multiple pathogenic mechanisms. The abnormal buildup of amyloid beta plaques and tau protein tangles plays a central role in neuronal damage and brain degeneration. Understanding these processes is essential for developing targeted therapies and early diagnostic tools to slow or halt disease progression.