Opazo Lab

Understanding cellular and molecular mechanisms

Alzheimer’s disease is characterised by the loss of brain connection (synapses) — the main correlate of cognitive deficits — at the early stages in the disease progression. Although much is known about the mechanisms underlying synaptic loss in Alzheimer’s, the repair and compensatory mechanisms within the neuron to counter and compensate for the loss remain largely unexplored.

The overarching aim of the Opazo Lab is to understand the cellular and molecular mechanisms underlying synaptic compensation and repair — with the ultimate goal of therapeutically harnessing these inherently protective mechanisms of the brain in order to delay the onset of clinical dementia.

Synaptic and neuronal compensation in Alzheimer’s disease

One of the most puzzling aspects of Alzheimer’s disease (AD) is that the accumulation of amyloid and tau pathology precedes the onset of clinical dementia by several decades. Dr Patricio Opazo believes that this delay corresponds to compensatory mechanisms implemented at all levels: first, at the synaptic level following synapse loss, and then at the neuronal and circuit level - and that the saturation of all these compensatory mechanisms mark the onset of clinical dementia.

Given that synaptic plasticity plays a central role in normal cognition as well as in the cognitive deficits associated to AD, Dr Opazo’s research programme aims to determine whether synaptic repair and compensation is critical to tolerate pathology in AD and thus, whether it may serve as the basis for cognitive resilience and future therapeutic opportunities.

Main objectives and research goals:

1. Investigate the synaptic compensatory and repair events triggered by the loss of synapses in Alzheimer’s disease models
2. Identify the molecular mechanisms underlying synaptic compensation and repair using RNA-seq and proteomic approaches
3. Boost synaptic compensatory and repair mechanisms to delay the onset of cognitive decline in Alzheimer’s disease animal models