Mechanistic role of mitochondria in Alzheimer's disease

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disease. Brains of AD patients contain amyloid beta (Aβ) plaques and tau tangles. Mitochondria play a large role in neuronal function by constantly providing energy, particularly at synapses. Mitochondrial function is decreased in AD patients. Decreased mitochondrial functioning impacts on synaps function, which could lead to neuronal damage and ultimately to memory loss and cognitive impairment in patients with AD. Ameloid beta, phosphorylated tau and mitochondrial function affect each other, but the sequence of cause and affect are not clear.

Relevant questions: What is the evidence that ameloid beta affects various mitochondrial functions and how? What is the evidence that phosphorylated tau affects mitochondrial function and how? What is the evidence that mitochndrial dysfunction can lead to plaque and tangle formation and how? How do ameloid beta and phosphorylated tau affect mitochondrial dynamics and how can this lead to AD? How can dysfunction of mitochondria increase plaque and tangle formation and how can this lead to AD? Ameloid beta, phosphorylated tau and mitochondrial function affect each other, but what is cause and consequence? How is metabolic health (or specific aspects of metabolic health such as insulin resistance) linked to AD? Which mechanisms underlie sex differences in AD susceptibility?

Aim: Define a specific research question related to one or more of the questions above. Write a logically structured report based on literature research question, focusing on specific proteins/mechanisms involved. Conclude and propose an experiment that brings this research on step further.