What is Alzheimer's Disease?
Alzheimer's disease is a progressive neurodegenerative disorder characterized by the decline in cognitive function and memory. It primarily affects the elderly and is the most common cause of dementia. Histologically, Alzheimer's disease is marked by specific pathological features, including the presence of
amyloid plaques and
neurofibrillary tangles.
What are Amyloid Plaques?
Amyloid plaques are extracellular deposits primarily composed of aggregated
beta-amyloid peptides. These peptides result from the improper processing of the amyloid precursor protein (APP). Over time, beta-amyloid peptides accumulate and form plaques, which disrupt cell-to-cell communication and activate immune responses, causing inflammation and neuronal damage.
What are Neurofibrillary Tangles?
Neurofibrillary tangles are intracellular accumulations of hyperphosphorylated
tau protein. Normally, tau supports microtubule stability within neurons. However, in Alzheimer's disease, tau becomes abnormally phosphorylated, leading to the formation of insoluble tangles. These tangles impede intracellular transport, contributing to neuronal dysfunction and cell death.
How are these Features Observed Histologically?
Histological examination of brain tissue in Alzheimer's patients reveals the presence of amyloid plaques and neurofibrillary tangles. Special staining techniques, such as
immunohistochemistry and silver staining, are used to visualize these pathological features. For instance, the
Bielschowsky stain is commonly used to highlight neurofibrillary tangles, while the
Congo red stain can identify amyloid plaques under polarized light, showing apple-green birefringence.
What Brain Regions are Affected?
Alzheimer's disease predominantly affects the
hippocampus and
cerebral cortex. The hippocampus is crucial for memory formation, and its degeneration correlates with memory loss. The cerebral cortex, responsible for higher cognitive functions, shows widespread neuronal loss and synaptic dysfunction, leading to impairments in reasoning, language, and perception.
What are the Cellular Changes Observed?
At the cellular level, Alzheimer's disease is associated with significant neuronal loss, synaptic degeneration, and gliosis.
Astrocytes and
microglia become activated in response to amyloid plaques, contributing to chronic inflammation and further neuronal injury. Additionally, there is a reduction in
cholinergic neurons in the basal forebrain, impacting neurotransmitter levels and cognitive function.
What are the Current Research Directions?
Current research in Alzheimer's disease is focused on understanding the molecular mechanisms underlying amyloid plaque and neurofibrillary tangle formation. Efforts are also directed toward developing biomarkers for early diagnosis and identifying potential therapeutic targets. Emerging treatments aim to reduce beta-amyloid production, inhibit tau phosphorylation, and modulate neuroinflammation. Advanced imaging techniques and
genetic studies are providing new insights into the pathophysiology of the disease.
