Alzheimer's Disease: Understanding Its Key Pathological Features and Neurological Impact

Alzheimer's disease is a progressive neurodegenerative disorder primarily affecting middle-aged and older adults. It stands as the most common cause of dementia worldwide, characterized by a gradual decline in cognitive functions such as memory, thinking, and reasoning. As the disease advances, individuals experience increasing difficulty with daily activities, eventually requiring full-time care. The condition not only impacts the individual but also places a significant emotional and financial burden on families and healthcare systems.

Structural Brain Changes in Alzheimer's Disease

One of the hallmark features of Alzheimer's is the visible atrophy of brain tissue. Over time, imaging techniques like CT and MRI scans reveal a noticeable reduction in brain volume and weight. This shrinkage is particularly prominent in critical areas responsible for memory and cognition, such as the hippocampus and temporal lobes. The deepening and widening of sulci (brain grooves) and gyri (ridges) are clear indicators of neuronal loss and tissue degeneration.

The hippocampus, essential for forming new memories, undergoes severe deterioration early in the disease process. Similarly, the temporal lobe—responsible for language comprehension and long-term memory—shows marked atrophy. These structural changes correlate directly with the worsening symptoms observed in patients, including confusion, disorientation, and impaired communication.

Core Pathological Hallmarks: Amyloid Plaques and Neurofibrillary Tangles

At the microscopic level, Alzheimer's disease is defined by two primary pathological abnormalities: amyloid plaques and neurofibrillary tangles. These formations disrupt normal brain function and contribute significantly to neuronal death.

Amyloid Plaques and Beta-Amyloid Accumulation

Amyloid plaques, also known as senile plaques, are clusters of misfolded proteins that accumulate in the spaces between nerve cells. They are primarily composed of beta-amyloid peptides, which result from the abnormal cleavage of the amyloid precursor protein (APP). These plaques are commonly found in regions such as the cerebral cortex, hippocampus, basal ganglia, thalamus, and amygdala.

The buildup of beta-amyloid triggers chronic inflammation and interferes with synaptic transmission, ultimately impairing communication between neurons. Over time, this disruption leads to widespread neural dysfunction and cell death, accelerating cognitive decline.

Neurofibrillary Tangles and Hyperphosphorylated Tau Protein

Neurofibrillary tangles are another defining feature of Alzheimer's pathology. Found inside neurons, these twisted fibers consist of hyperphosphorylated tau protein. In healthy brains, tau stabilizes microtubules—structures that transport nutrients within nerve cells. However, in Alzheimer's, excessive phosphorylation causes tau to detach and clump together, forming tangles that block cellular transport and lead to neuronal collapse.

The spread of tau pathology often follows a predictable pattern, starting in the entorhinal cortex and progressing to the hippocampus and beyond. This progression closely mirrors the clinical stages of the disease, making tau an important biomarker for tracking Alzheimer's severity.

Additional Neuropathological Observations

Beyond plaques and tangles, Alzheimer's involves other significant neurological changes. There is substantial loss of neurons and synapses, particularly in regions linked to learning and memory. Additionally, glial cells—such as astrocytes and microglia—undergo reactive changes, contributing to neuroinflammation.

While glial cells normally support neuronal health, in Alzheimer's they become overactivated in response to amyloid deposits, releasing inflammatory cytokines that can further damage surrounding tissue. This chronic state of inflammation exacerbates neurodegeneration and creates a toxic environment in the brain.

In summary, Alzheimer's disease is far more than simple memory loss—it is a complex neurological disorder rooted in distinct pathological processes. Understanding these mechanisms, including brain atrophy, amyloid plaque formation, tau tangle development, and neuroinflammation, is crucial for developing effective treatments and early diagnostic tools. Ongoing research continues to explore ways to halt or reverse these changes, offering hope for future therapies.