Question

2. Cytoskeleton of neuron is very important to neuron function. Alzheimer’s disease is an example of central nerve system disease related to cytoskeleton dysfunction. How are proteins of “tau” and “amyloid” related to Alzheimer’s disease (AD)? Please elaborate this question as much as possible.

Answer 1

Answer-Alzheimer disease is a neurodegenerative disease,being the most common cause of dementia in older adults.The disease usually becomes clinically apparent as insidious impairment of higher cognitive function s.As the disease progresses,deficit in memory,visuospatial orientation, judgement , personality and language emerge.Over a course of five to ten years ,the affected individual becomes profoundly disabled ,mute,and immobile.

Role of A beta: Amyloid precursor protein (APP) is a transmembrane protein and can be processed by two pathways:

a) cleavage by alpha secretase and gamma Secretase produces a harmless soluble peptide(Nonamyloidogenic alpha secretase pathway)

b) cleavage by beta amyloid converting enzyme(BACE) and gamma Secretase releases pathogenic A beta peptide(Amyloidogenic beta Secretase pathway)

• ​​​​​A beta aggregate are directly neurotoxic and it will induce synaptic damage of nucleus basalis of mayernet. This will decrease acetylcholine neurotransmitter and cause dementia and mental retardation.
• Familial forms of Alzheimer's disease are related to mutation in APP(Amyloid precursor protein) or alteration in its processing.

Role of 'tau': Tau is a microtubule-associated protein in axons in association with the microtubular network. With the development of tangles in Alzheimer disease, it shifts to a somatic-dendritic distribution, becomes hyperphosphorylated, and loses the ability to bind to microtubules. The aggregates of tau protein elicit a stress response and second, the microtubule stabilizing function of tau protein is lost, leading to neuronal damage.