# Amyloid Beta Oligomers as Early Triggers of Neuronal Cytoskeleton Dysfunction in Alzheimer’s Disease

## TL;DR

This paper reviews how amyloid beta oligomers disrupt the neuronal cytoskeleton early in Alzheimer’s disease, contributing to cognitive decline before significant neuron death occurs.

## Contribution

The paper highlights the early role of amyloid beta oligomers in triggering cytoskeletal dysfunction as a novel perspective in Alzheimer’s disease pathogenesis.

## Key findings

- Amyloid beta oligomers disrupt microtubules and actin dynamics through LIMK–cofilin signaling.
- Neurofilament light chain levels rise as an early biomarker of axonal damage in Alzheimer’s.
- Cytoskeletal changes occur before extensive neuronal death, indicating early disease progression.

## Abstract

Alzheimer’s disease (AD) is characterized by progressive cognitive decline, with amyloid beta oligomers (AβOs) emerging as the most neurotoxic species and acting as early triggers of cellular alterations. Before the appearance of other protein aggregates, AβOs disrupt the dynamics and stability of the neuronal cytoskeleton, a structure essential for maintaining neuronal morphology, axonal transport, and synaptic plasticity. Experimental evidence demonstrates that AβOs promote microtubule disassembly, Tau hyperphosphorylation, reduced kinesin levels, impaired axonal transport, and alterations in actin dynamics through the LIMK–cofilin signaling pathway. In addition, increased levels of neurofilament light chain have been identified as an early biomarker of axonal damage. Notably, these cytoskeletal disturbances arise in the absence of extensive neuronal death, underscoring the cytoskeleton as a critical early target in AD pathogenesis. In this review, we analyze cytoskeletal alterations induced by AβOs in neurons and discuss how these changes may contribute to disrupted neuronal communication, a defining early hallmark of AD pathology.