LECTURE 5 Flashcards
What is the most important hypothesis for the pathogenetic process of AD? How can this hypothesis be proven?
The amyloid cascade hypothesis proposes that the accumulation and deposition of amyloid-beta (Abeta) peptides in the brain play a central role in the development and progression of Alzheimer’s disease. According to this hypothesis, the abnormal production and aggregation of Abeta peptides initiate a cascade of events, including the formation of plaques, neuroinflammation, tau protein abnormalities, and ultimately neuronal dysfunction and cognitive decline. Targeting Abeta accumulation and its downstream effects is a key focus in the development of therapies for Alzheimer’s disease.
What are the pathological hallmarks of AD? What are important therapeutic targets for AD?
Amyloid plaques: These are abnormal clumps of beta-amyloid protein that accumulate between neurons. Amyloid plaques are formed by the aggregation of amyloid-beta peptides and are one of the characteristic features of Alzheimer’s disease.
Neurofibrillary tangles: These are twisted fibers composed of hyperphosphorylated tau protein, which forms within neurons. Neurofibrillary tangles disrupt the normal functioning of neurons and contribute to their degeneration.
important therapeutic targets for Alzheimer’s disease include:
Amyloid-beta: Targeting the production, aggregation, or clearance of amyloid-beta is a major therapeutic focus. Strategies include reducing the production of amyloid-beta, promoting its clearance, or directly targeting amyloid plaques with antibodies or other agents.
Tau protein: Given the role of abnormal tau in the formation of neurofibrillary tangles, therapeutics targeting the reduction of tau pathology are being explored. This includes inhibiting tau phosphorylation, preventing tau aggregation, and promoting the clearance of abnormal tau.
Combined therapeutic strategies.
Why is tau an important therapeutic target?
Tau-pathology progression correlates strongly with the progression of symptoms of AD.
Tau-mutations are causally linked to neurodegenerative disorders
Tau-aggregates: different neurodegenerative diseases (Tauopathies)
Indications for a self-propagating effect of Tau-pathology: spreading of tau-pathology.
Why are models with combined amyloid and tau-pathology important?
Models with combined amyloid and tau pathology are important because they closely mimic the complexity of Alzheimer’s disease, allowing for a better understanding of the disease mechanisms and the development of effective treatments that can deal with the Tau pathology and abeta at the same time.
