Alzheimer’s disease is a progressive neurodegenerative disorder that gradually damages brain cells, leading to a decline in memory, thinking skills, and other cognitive abilities. It represents the most common form of dementia, affecting millions globally. Homeostasis refers to the body’s ability to maintain stable internal physical and chemical conditions despite external changes. This intricate balance is essential for optimal cellular functioning. Alzheimer’s disease fundamentally disrupts this delicate homeostatic equilibrium within the brain.
Disruption of Cellular Energy and Signaling
The brain maintains high energy demands, primarily relying on glucose as its main energy source. In Alzheimer’s, the brain’s ability to metabolize glucose and produce energy is impaired, leading to energy deficits within neurons. Mitochondrial dysfunction significantly contributes to this energy shortage, as mitochondria are the primary sites for energy production.
Cellular communication also becomes disrupted. Neurons experience dysregulation of ion channels, particularly calcium ions. Abnormal calcium signaling alters neuronal excitability and impacts brain function. This imbalance affects how nerve cells transmit signals, contributing to neuronal dysfunction.
Imbalances in key neurotransmitters, chemical messengers for brain cells, are observed. Acetylcholine, crucial for memory and learning, is significantly reduced. Glutamate, also involved in learning and memory, can be dysregulated, sometimes leading to overactivation of certain receptors. These imbalances contribute to difficulties in cognitive functions like memory and attention.
The disease also harms synaptic function and plasticity, fundamental for learning and memory. Synapses are the connections between nerve cells where communication occurs. Impaired synaptic plasticity compromises the brain’s ability to strengthen or weaken these connections, directly affecting new memory formation and retention of learned information.
Impaired Protein and Waste Clearance
Alzheimer’s disease is characterized by the accumulation of abnormally folded proteins in the brain, which disrupts cellular function. Amyloid-beta misfolds and clumps to form plaques outside neurons, interfering with cell communication and contributing to neuronal damage.
Another protein, tau, also undergoes abnormal changes. Normally, tau stabilizes microtubules, structures that are part of the cell’s internal transport system. In Alzheimer’s, tau becomes hyperphosphorylated, detaches from microtubules, and aggregates into neurofibrillary tangles inside neurons. These tangles block the neuron’s transport system, impairing nutrient transport.
Cellular waste disposal systems, which clear damaged proteins, become inefficient. Mechanisms like the ubiquitin-proteasome system and autophagy, responsible for breaking down cellular waste, are compromised. This failure allows toxic proteins to accumulate within brain cells.
The glymphatic system, a specialized brain waste clearance system, also experiences impaired function. This system facilitates cerebrospinal fluid flow to remove metabolic waste products, including amyloid-beta and tau. Reduced efficiency contributes to the build-up of these pathological proteins, exacerbating progression.
Neuroinflammation and Immune Dysregulation
The brain’s immune system, particularly glial cells like microglia and astrocytes, plays a complex role in Alzheimer’s disease. Initially, these cells can be protective, clearing debris and supporting neurons. However, in Alzheimer’s, they often become chronically activated and shift to a detrimental state.
This chronic activation leads to neuroinflammation, an inflammatory response within the central nervous system. Activated microglia and astrocytes release pro-inflammatory cytokines and chemokines. These molecules create a sustained inflammatory environment, damaging neurons and contributing to protein aggregation. This creates a self-perpetuating cycle where inflammation exacerbates pathology, and pathology fuels more inflammation.
The blood-brain barrier, a protective boundary, can also become compromised. Disruption allows peripheral immune cells and harmful substances to infiltrate the brain. This influx intensifies inflammation and contributes to neuronal injury, further destabilizing the brain.
Consequences of Imbalance
The combined effects of cellular energy deficits, toxic protein accumulation, and chronic neuroinflammation lead to widespread neuronal dysfunction and eventual death in Alzheimer’s disease. Brain regions responsible for memory, learning, and cognitive processing, such as the hippocampus and cerebral cortex, are particularly affected.
Ultimately, the breakdown of homeostasis drives the cognitive decline and neurodegeneration characteristic of Alzheimer’s. The progressive loss of neuronal function and brain cell death result in severe memory loss, disorientation, and behavioral changes.