Alzheimer's disease - plaques, tangles, causes, symptoms & pathology

Summary

This video explains the nature of dementia, focusing on Alzheimer's disease as its most common cause. Alzheimer's is a neurodegenerative condition, where plaques and tangles form in the brain, leading to neuronal damage and memory loss. The video describes how amyloid plaques and tau protein tangles disrupt brain cell communication, contributing to dementia symptoms. It also discusses genetic risk factors, like the APOE-e4 gene and mutations linked to early-onset Alzheimer's. The progression of Alzheimer's leads to severe cognitive decline, and although no cure exists, the video touches on current treatments aimed at slowing its advancement.

Takeaways

• 🧠 Dementia describes a set of symptoms such as memory loss and difficulty learning new information, often affecting independent functioning.
• 🔄 Alzheimer disease is the most common cause of dementia and is considered a neurodegenerative disease, primarily affecting the brain's cortex.
• 🧬 The formation of amyloid plaques and neurofibrillary tangles are key factors in the progression of Alzheimer disease.
• 🧩 Amyloid precursor protein (APP) in neurons can be broken down by enzymes, but when beta-secretase and gamma-secretase act together, it forms beta-amyloid plaques.
• ⚠️ Beta-amyloid plaques disrupt neuron-to-neuron signaling and can cause inflammation, which may lead to neuron damage and brain function impairment.
• 🔗 Tau proteins in neurons help stabilize microtubules, but when they malfunction due to amyloid buildup, they form tangles inside the neuron, further hindering neuron function.
• 🔍 Alzheimer disease causes brain shrinkage, narrowing of the gyri, widening of the sulci, and enlargement of the brain's ventricles.
• 👵 Alzheimer’s can be sporadic or familial, with sporadic Alzheimer’s being the most common and its risk increasing with age.
• 🧬 Genetic factors, such as the APOE-e4 allele or mutations in PSEN-1 and PSEN-2 genes, are linked to an increased risk of developing Alzheimer disease, especially in familial cases.
• 🩺 There is currently no cure for Alzheimer disease, and diagnosis is challenging, often requiring exclusion of other causes of dementia. Medications offer limited benefits.

Q & A

What is dementia, and how is it related to Alzheimer disease?

Dementia is a term used to describe a set of symptoms, such as memory loss and difficulty with cognitive functions, rather than a specific disease. Alzheimer disease is the most common cause of dementia and is a neurodegenerative condition that leads to the progressive loss of neurons in the brain.

What are the two main factors contributing to the progression of Alzheimer disease?

The two major factors are plaques and tangles. Plaques consist of beta-amyloid proteins that accumulate outside neurons, disrupting signaling, while tangles are formed inside neurons when tau proteins become dysfunctional and clump together, damaging the microtubules that support cellular structure.

How do beta-amyloid plaques form in the brain?

Beta-amyloid plaques form when amyloid precursor protein (APP) is broken down by beta secretase and gamma secretase, producing an insoluble fragment called amyloid beta. These amyloid beta monomers stick together to form clumps or plaques, which interfere with neuron communication and may cause inflammation.

What role does the tau protein play in Alzheimer disease?

Tau proteins normally stabilize microtubules within neurons, but in Alzheimer disease, they become phosphorylated, change shape, and form neurofibrillary tangles. These tangles disrupt the microtubules, impairing neuron function and contributing to cell death.

What is the difference between sporadic and familial Alzheimer disease?

Sporadic Alzheimer disease typically has a late onset and is likely caused by a combination of genetic and environmental factors, while familial Alzheimer disease is early-onset and inherited, usually due to mutations in specific genes such as PSEN-1, PSEN-2, or trisomy 21 (Down syndrome).

How does the APOE-e4 allele influence the risk of developing Alzheimer disease?

The APOE-e4 allele is associated with a higher risk of developing Alzheimer disease because it is less effective at breaking down beta-amyloid, leading to increased plaque formation. Individuals who inherit one or two copies of this allele have a greater likelihood of developing the disease.

Why do people with Down syndrome have a higher risk of developing early-onset Alzheimer disease?

People with Down syndrome have an extra copy of chromosome 21, which contains the gene responsible for producing amyloid precursor protein (APP). The increased production of APP leads to more amyloid plaques, which contributes to the early onset of Alzheimer disease, typically by age 40.

What are some of the early and late-stage symptoms of Alzheimer disease?

Early-stage symptoms include short-term memory loss and difficulty recalling recent events. As the disease progresses, individuals may lose motor skills, experience difficulty with language, and eventually lose long-term memory, becoming disoriented and bedridden.

What are the brain changes observed in Alzheimer disease?

In Alzheimer disease, the brain undergoes atrophy, where the gyri (ridges) shrink, the sulci (grooves) widen, and the ventricles (fluid-filled spaces) enlarge. These changes occur as neurons die and the brain loses mass.

Is there a cure for Alzheimer disease?

Currently, there is no cure for Alzheimer disease. While some medications can provide small benefits, none are capable of stopping the progression of the disease. Diagnosis is also challenging and can only be definitively confirmed through a brain biopsy after death.