Viewing a single comment thread. View all comments

FlowersForAlgerVon t1_iu5e8ax wrote

Reply to comment by wrhollin in Does the cerebral spinal fluid of people with Alzheimer's have a notably different pH from 'normal' people's? by wrhollin

No problem, happy to answer your questions! Tau and Abeta are rather complex proteins that have amino acid residues that carry charges allowing it to take certain shapes. The pathogenic form of tau is the hyperphosphorylated version, where tau carries more phosphate groups (negatively charged) allowing it to stick to each other and form what we call neurofibrillary tangles inside a neuron. How the ionization states and interaction with itself is affected by pH environments, I've no clue. For Abeta, the larger protein has been shown to more readily form these plaques due to a larger surface area, I'm not sure how ionization states affect the formation there either.

​

That's about the best I can answer your question haha.

​

Edit: Tangentially, the pH environment can affect enzyme ionization states that changes the shape enough that it increases production of these 'large' Abeta oligomers, leading to more accumulation of plaques.

144

notjeffre t1_iu7gab6 wrote

that little bit you mentioned about the effect of pH environment on the ionization & interaction of disordered proteins is exactly what I’ve been working on for my biophysics phd research lol

(not tau, but another intrinsically disordered protein. its not often I see the last five years of my life succinctly mentioned in a single sentence on my reddit scroll)

48

PyroDesu t1_iu7rkq1 wrote

> The pathogenic form of tau is the hyperphosphorylated version, where tau carries more phosphate groups (negatively charged) allowing it to stick to each other and form what we call neurofibrillary tangles inside a neuron.

What causes the hyperphosphorylation, out of curiosity?

5