# Form follows function: morphology as a map of mechanisms in neurodegenerative disease pathology

## TL;DR

This paper argues that the shapes and structures seen in brain diseases reveal important clues about the biological processes causing them.

## Contribution

A novel framework connecting specific pathological morphologies to underlying cellular and biophysical mechanisms in neurodegeneration.

## Key findings

- Morphological features like vacuoles and amyloid plaques reflect distinct cellular processes and material states.
- Pathology shapes are shown to be direct readouts of protein self-assembly and proteostasis mechanisms.
- The paper proposes that morphology is central to understanding disease progression, not just a side effect.

## Abstract

Across neurodegenerative diseases, the shape and spatial organization of pathology carry rich mechanistic information. Vacuoles, spongiosis, oligodendroglial coiled bodies, dendritic dystrophic neurites, amyloid plaque compactness, and phase-separated droplets each reflect distinct cellular identities, subcellular compartments, trafficking pathways, and biophysical material states. Here, I synthesize morphological signatures across neurodegenerative diseases to propose a framework that links morphology to mechanism. Morphology is neither incidental nor merely descriptive. Rather, it is a readout of the basic mechanisms that govern self-assembly of proteins into aggregates, the cell’s attempts at proteostasis (clearance, sequestration, and transport), and the failure that ensues.