Mechanisms and secrets of Alzheimer's disease: exploring the brain

Summary

This video explores the scientific understanding of Alzheimer's disease, first described by Alois Alzheimer in 1907. It highlights the two primary brain lesions associated with the disease—amyloid plaques and neurofibrillary tangles—and their roles in neuronal degeneration. The video explains how these lesions form and spread in the brain, and their connection to cognitive symptoms like memory loss and language problems. Despite advances in research, questions remain about the precise mechanisms driving the disease. Current research focuses on understanding the relationship between amyloid-beta and tau proteins and aims to uncover new ways to treat or prevent Alzheimer's.

Takeaways

• 😀 Alzheimer's disease was first described in 1907 by German psychiatrist Alois Alzheimer, who identified two types of brain lesions: amyloid plaques and neurofibrillary tangles.
• 🧠 The brain consists of neurons that are interconnected by synapses, enabling communication. Alzheimer's disease disrupts this communication through abnormal protein accumulations.
• 🔬 In Alzheimer's, amyloid plaques (made of amyloid beta protein) and neurofibrillary tangles (made of tau protein) form years before the appearance of symptoms, contributing to cognitive decline.
• 🧩 Amyloid beta protein is usually processed by enzymes and cleared from the body, but in Alzheimer's disease, this process becomes imbalanced, leading to plaque formation.
• ⚙️ Neurofibrillary tangles are formed when tau protein, which normally stabilizes microtubules in neurons, becomes defective and detaches, causing the neuron’s structure to disintegrate.
• 🌍 Amyloid plaques and neurofibrillary tangles spread through the brain in different patterns, with tangles affecting memory and cognitive regions first, while plaques follow a different trajectory.
• ⏳ The presence of both amyloid plaques and neurofibrillary tangles is necessary for the development of Alzheimer's disease, but the order in which they form is still debated.
• 💡 Scientific research suggests that toxic oligomers of amyloid beta, which appear before plaques, may damage neurons by disrupting their communication, leading to the formation of tangles.
• ❓ The exact molecular mechanisms leading to Alzheimer's dementia, and the role of genetics and environmental factors in its development, are still not fully understood.
• 🧬 Despite challenges, continued research into Alzheimer's disease is uncovering new insights that bring hope for potential treatments or even a cure.

Q & A

Who first described Alzheimer's disease and when?

Alzheimer's disease was first described in 1907 by German psychiatrist Alois Alzheimer, who conducted a histopathologic study of the brain of his patient, Auguste D.

What were the two key lesions discovered by Alois Alzheimer in the brain of his patient?

Alois Alzheimer discovered two key lesions in the brain: amyloid plaques and neurofibrillary tangles.

What are amyloid plaques composed of in Alzheimer's disease?

Amyloid plaques are composed of amyloid-beta proteins, which form insoluble fibrils that accumulate on the surface of neurons.

How does amyloid-beta normally function in the brain, and what goes wrong in Alzheimer's disease?

Normally, amyloid-beta is cleaved from amyloid precursor protein (APP) by enzymes and cleared from the body. In Alzheimer's disease, this process is disrupted, leading to an imbalance where amyloid-beta accumulates and forms plaques.

What role does tau protein play in healthy neurons, and what happens to it in Alzheimer's disease?

Tau protein stabilizes the microtubules in the neuron’s skeleton, aiding in cellular function. In Alzheimer's, tau becomes defective, detaches from microtubules, and forms twisted filaments, leading to neurofibrillary tangles and neuronal degeneration.

What is the progression pattern of neurofibrillary tangles in the brain?

Neurofibrillary tangles first develop in the hippocampus, a region vital for memory and learning, and then spread throughout the brain following a centrifugal pattern, leading to atrophy and global dysfunction.

How do amyloid plaques spread in the brain compared to neurofibrillary tangles?

Amyloid plaques develop initially in the cortex, then spread to the hippocampus and other brain regions following a centripetal pattern. Unlike neurofibrillary tangles, the progression of amyloid plaques does not directly correlate with the symptoms of Alzheimer's disease.

What are oligomers, and why are they thought to be important in the development of Alzheimer's disease?

Oligomers are smaller forms of amyloid-beta that appear before amyloid plaques fully form. They are toxic to neurons and interfere with synaptic communication, possibly contributing to the development of neurofibrillary tangles and Alzheimer’s symptoms.

What is the current state of clinical trials targeting amyloid plaques in Alzheimer's disease?

Many clinical trials aimed at reducing amyloid plaques have failed to effectively eradicate the disease. Research has shifted focus to understanding the role of smaller amyloid-beta oligomers in the disease's progression.

What are the main areas of ongoing research in Alzheimer's disease?

Ongoing research focuses on understanding the molecular mechanisms of Alzheimer's, the relationship between amyloid-beta and tau proteins, and the roles of genetics and environmental risk factors. Scientists are exploring potential therapies to prevent or treat the disease.