Irina Alafuzoff's projects in Neuropathology

The material that we study is human tissue, brain or other organs, that has been obtained post-mortem (neurodegeneration and vascular pathology) or during surgical procedure (primary brain tumours). The methods applied include among others histology, immunohistochemistry and morphometry

Neurodegenerative diseases

One of the major events in neurodegeneration is misfolding of proteins that tend to accumulate in the cells or matrix. Misfolding of proteins increases with aging. Accumulation of misfolded proteins leads to functional disturbances seen as various movement disorders or cognitive impairment/dementia.

Based on current knowledge the most common form of neuronal degeneration is the hyperphosphorylation of the tau (HPtau) protein followed in incidence by alteration of beta-amyloid, alpha-synuclein and transactive DNA binding protein 43. Recently it has been suggested that these protein alterations have a certain initiation site and the protein alterations have been suggested to progress in a prion like manner, i.e. after initiation nothing can halter their progress to neocortical regions.

Recently it has been implicated that one misfolded protein might initiate misfolding of another protein, i.e. seeding. Further it has been suggested that the initiation and/or the progression of protein alteration might be influenced by systemic conditions such as middle age hypertension, diabetes, cardiovascular disease, low BMI. All these conditions have been implicated as risk factors for neurodegenerative disorders in epidemiological studies.

In the research team we are addressing the following questions: initiation site of neuronal degeneration, incidence of certain neuronal degeneration, progression pattern and associated alterations such as astrogliosis, microgliosis, seeding of misfolding of proteins.

Vascular brain pathology

With aging the cardiac function as well as the vessels display age related changes that ultimately lead to various extent of circulatory failure. Brain tissue alterations related to insufficient circulation are common but poorly investigated. A brain infarct can be seen as a defined lesion. To assess brain tissue with diffuse neuronal loss, loss of oligodendrocytes or activation of astrocytes or microglia that is initiated by various severity of ischemia/anoxia is more difficult.            

Briefly, the research team is studying primary protein alteration to be seen in neurons, astrocytes, oligodendrocytes or microglia at hypoxia/anoxia.