Can discrepancy between FD and FC be used to make assumptions about neurodegenerative progression?


I realize the title is a bit convoluted, so allow me to explain what I mean in detail…

I’m studying 2 fiber bundles interconnected through a synapse, and I’m trying to figure out which bundle suffers from degeneration first and which bundle degenerates as a result of trans-synaptic/trans-neural degeneration (basically, secondary to the first bundle’s degeneration).

According to Raffelt et al, 2017:

…following axon loss, the additional extra-axonal space may be persistently filled with extracellular matrix and cells related to inflammation or gliosis (as shown in Fig. 1a). However, it’s also feasible that after debris are cleared, the fibre bundle becomes atrophic (white matter atrophy is a feature of many diseases including Alzheimer’s disease and Motor Neurone Disease).

Now, what I gather from this statement is that in neurodegenerative diseases, FD is expected to decrease first (indicating axonal loss), followed eventually by a decrease in FC (indicating a macro-scale atrophy of the whole bundle).

Based on this idea, if I were to find a loss of both FD and FC in one of my studied bundles, but only a loss of FD in the other, would it make sense to assume that degeneration starts in the bundle with FD and FC loss, followed by the one with FD loss only??

I hope my question makes sense. I can make a few rough sketches if my post is not clear enough. I realize the idea is a bit “out there”, so I wanted to run it by anyone here how’s willing to listen.

Thnak you for the constant support!