Alzheimers Flashcards
What are the symptoms?
Memory deficits (loss of memory), loss of function (memory and insight), personality changes (apathy and social withdrawal)
What is Alzheimers?
Progressive neuro degenerative brain disorder which leads to memory loss, motor deficits and eventual death. Most common neuro degenerative disorder (Nestor et al. 2004)
How does it differ from ageing?
Shrinkage of the brain tissue and synaptic decrease is normal in ageing but the loss of function and the progressive severity is what makes Alzheimer’s different
What is the beta-amyloid hypothesis?
Gene encodes Amyloid Precursor Protein (APP) which is cut into first by Beta secretase then by Gamma-secretase to form long (42 amino acids) and short (40 amino acids). In normal individuals there are only 5-10% but due to deficits in gamma-secretase this rises to 40% in Alzheimer’s patients.
How are neuritic plaques formed?
Due to high frequency of long form, folds improperly and aggregates into neuritic plaques. Dense core of beta amyloid forms surrounded by degenerating axons and dendrites, and activated microglia and reactive astrocytes. Degenerating axons and dendrites are engulfed in phagocytes cells and the dense core of beta amyloid is left
How is long form usually disposed of?
Long form beta amyloid is usually tagged and transported to the protosomes and destroyed. However in high frequencies this is not possible.
What did Nestor et al (2004) show about how this relates to the symptoms?
Formation of neuritic plaques transport to areas such as the hippocampus resulting in symptoms such as memory loss
Who else showed the connection between neuritic plaques and symptoms?
Matteson et al (2004) showed that increased beta-amyloid deposition contributes directly to the demise of neurons. Increasing the risk of exctitoxcity, metabolic stress and oxidative stress.
Who disagreed with the beta amyloid hypothesis through pathological examinations?
Nagy et al. (1995) pathological examinations of beta amyloid show no correlation between fibrillary amyloid deposit and the degree of dementia and neurodegeneration
Who disagreed with the beta amyloid through rat studies?
Transgenic mice that over expressed human APP show that learning and memory deficits and impairments in synaptic transmission occur in the absence of amyloid deposits (Chishiti et al 2010) and no neuronal death (Duff, 1998)
How does beta amyloid affect calcium regulation?
Affects calcium regulation (involved in cell death) and induces oxidative stress (imbalance between reactive oxygen species and the systems ability to detoxify the reactive indeterminides). Impairs calcium membrane pumps and increases calcium intake through voltage dependent channels.
What did further work show?
Laferi and Oddo (2005) showed that despite extensive development of amyloid deposits on other aspects of the neuropathology were found. Maybe due to the short life of a mouse?
What newer idea is taking over from the beta amyloid hypothesis?
Kostinah and kostinah (2001) showed that soluble amyloid (freely diffuse through the brains parenchyma) was better correlated with severity of the disease than amyloid plaques.
What did the soluble amyloid hypothesis find in rat models?
Zebrinah et al (2004) found that soluble beta amyloid in mice over expressing human APP was highly correlated with spatial and learning deficits
How are researchers using the immune system as a treatment?
Immune system to generate antibodies against beta amyloid to promote its removal adaptive response aimed at neural plasticity and survival (Matteson 2004)
