Alzheimer's Disease Mechanisms Overview

Study Notes

Overview of Alzheimer's Mechanisms

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain.
These abnormal protein aggregates disrupt neuronal communication and lead to neuronal death, resulting in cognitive decline, memory loss, and behavioral changes.

Amyloid Plaques

Amyloid plaques are extracellular deposits primarily composed of beta-amyloid (Aβ) peptides.
Aβ peptides are generated from the amyloid precursor protein (APP) through sequential enzymatic cleavage by β-secretase and γ-secretase.
The accumulation of Aβ peptides disrupts neuronal function and promotes inflammation, contributing to neuronal damage.
Mutations in APP, presenilin 1 (PS1), and presenilin 2 (PS2) genes are associated with familial forms of Alzheimer's disease, often resulting in increased production of Aβ peptides.

Neurofibrillary Tangles

Neurofibrillary tangles are intracellular aggregates of hyperphosphorylated tau protein.
Tau protein normally stabilizes microtubules within neurons.
Hyperphosphorylation of tau disrupts its normal function, causing it to detach from microtubules and aggregate into tangles.
These tangles interfere with axonal transport and neuronal communication, further contributing to neuronal dysfunction.
Mutations in the tau gene (MAPT) can cause familial forms of AD and are linked to earlier onset and more severe disease progression.

Genetic Predisposition

Familial AD cases account for a small proportion of total cases.
However, genetic factors play a role in sporadic AD as well, influencing susceptibility.
Genes such as APOE, and additional genes are implicated in the risk of developing AD through various mechanisms.
Variations in these genes influence Aβ metabolism, tau phosphorylation, and neuron resilience.

Other implicated factors in Alzheimer's Disease

The role of oxidative stress and inflammation in neuronal damage and AD progression is increasingly recognized.
Oxidative stress can damage cell components, including proteins and lipids.
Inflammatory responses contribute to neuroinflammation, which is a feature of AD, resulting in neurons dysfunction.
Environmental factors like diet and lifestyle may further influence susceptibility to AD by affecting the risk factors already discussed.

Current Therapeutic Strategies

Current therapies primarily focus on managing symptoms and slowing the disease progression, rather than curing it.
Some drugs aim to reduce Aβ accumulation and aggregation.
Other approaches target tau phosphorylation and aggregation.
Research continues to explore novel therapeutic targets and strategies.

Description

Explore the underlying mechanisms of Alzheimer's disease, focusing on the formation of amyloid plaques and neurofibrillary tangles. Understand how these proteins interfere with neuronal communication and lead to cognitive decline. This quiz will provide insights into the biological processes that contribute to this progressive disorder.