University of Leicester
2022SANTIAGO MUGICA E_PhD.pdf (13.54 MB)

The tubulin code in vascular dementia and Alzheimer’s disease

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posted on 2022-08-15, 12:21 authored by Estibaliz Santiago Mugica

Vascular dementia and Alzheimer’s disease are the two most common forms of dementia. While vascular dementia is caused by reduced blood flow to the brain, Alzheimer’s disease patients have amyloid and tau protein deposits in their brain. Although these two dementias have different etiologies, they share some similarities in their pathophysiology, such as altered hemodynamics, morphological and cellular changes, including synaptic proteins loss. 

This thesis builds on a previous work that reported a non-significant decrease of tubulin together with a loss of neuronal cell volume with loss of soluble tau protein in the temporal, but not the frontal cortex of patients with vascular dementia.

In this thesis, we hypothesise that molecular changes in tubulin may result in changes in other cytoskeletal proteins and precede the neuronal cell loss observed in dementia. To further explore this hypothesis, this thesis studies not only various isotypes of tubulin, but also several post-translational modifications of tubulin. In addition, the level of microtubule associated proteins were also quantified, and the processes of regeneration and degeneration investigated.

This thesis provides evidence of a distinct pattern in the level of tubulin depending on the isotype and dementia being studied. Furthermore, we show that VaD patients show significantly lower levels of tyrosinated tubulin in the frontal lobe when compared to controls. We also found lower levels of tau and MAPA2 in the frontal lobe of Alzheimer’s disease patients when compared to controls, together with lower levels of MAP6 in both vascular dementia and Alzheimer’s disease subjects in the temporal lobe.



Elizabeta B. Mukaetova-Ladisnka; Ruth Luthi-Carter; Flaviano Giorgini

Date of award


Author affiliation

Department of Neuroscience, Psychology and Behaviour

Awarding institution

University of Leicester

Qualification level

  • Doctoral

Qualification name

  • PhD