Institute of Neuroscience

Staff Profile

Mary Johnson

Technician (Research)

Background


I am currently employed on the Alzheimer Society Project The influence of cortical neurodegenerative pathology on white matter integrity with Professor Attems and Dr McAleese, in 2017 I will commence a role on the Alzheimer Society Project Pyroglutamylated amyloid beta in Alzheimer's and Lewy body disease with Professor Attems and Dr Walker. I have 36 years of experience in neurodegenerative research, with expertise in histology, histochemistry, immunocytochemistry, fluorescence staining, image analysis and basic neurochemistry.

Research

Collaborations

Ludwig Aigner :Salzberg

Distribution of 5LOX in the hippocampus of LBD, AD, PDD and controls and its relation to pathological features.

 The pro-inflammatory enzyme 5-lipoxygenase (5-LOX) is involved in chronic inflammatory diseases in the periphery. It is an enzyme which is also expressed in the brain, with particularly high levels in the hippocampus, its expression increases during ageing and in neurodegenerative disorders. Several lipoxygenases, including 5-LOX and 12/15-LOX, are elevated in brain tissues of AD subjects and Abeta-overproducing transgenic mice, inhibition of 5-LOX reduces Abeta production in vitro and is protective against Abeta-mediated neurotoxicity. This suggests 5-LOX plays a role in AD and is a potential target for novel therapeutic agents, Its localization and association with the hallmark lesions of the disease, b-amyloid (Ab) plaques and neurofibrillary tangles (NFTs), has shown a relationship between elevated intracellular 5-LOX and hallmark AD pathological lesions which provide evidence that neuro-inflammatory pathways contribute to the pathogenesis of AD. 

This study aims to look at 5LOX and its relationship in the hippocampus to the neuropathological hallmarks of other neurodegenerative diseases such as Parkinson’s disease with dementia (PDD) and Dementia with Lewy Bodies (DLB).

 Ludwig Aigner :Salzberg

Colocalisation of Doublecortin and other neuronal markers with A Beta plaques.

 The finding of cells, expressing this doublecortin marker normally only expressed on neuronal progenitors could play an important role in the process of regeneration. Newly formed neurons or progenitors at sites of a lesion (as known from stroke) or cells that start to express this marker after a disease specific stimuli, e.g. increase in Abeta (soluble or plaques) could be a possible treatment option to overcome the neuronal loss known in AD. Furthermore, if these cells are somehow related to Abeta plaque clearance, and their function is to help the age-related fatigued microglia to get rid of the Abeta plaque burden, this could be a new platform of AD treatment.

Conversely an inhibition of this cell type and its effect on AD pathology will be investigated and evaluated to obtain more knowledge of the origin and of course function of these cells. Currently it is suggested these cell type, highly expressing DCX, maybe has its origin in the periphery (blood) and maybe is attracted by Abeta. Further study of the functional relevance of this protein, and its role in axonal outgrowth/growth cone formation is required.

 

Jochen Herms:  Munich

Synaptic density in age associated neurodegneration

 It is generally assumed that in age associated neurodegnerative diseases the number of connections between nerve cells, i.e. the synapses, is considerably reduced. This reduction of synapses is likely to play an important role in the development of dementia symptoms such as forgetfulness. Looking down the microscope we also see depositions of aggregated proteins in the brain tissue of individuals with dementia; hyperphosphorylated tau, amyloid beta and alpha synuclein are the most frequent types of these aggregated proteins. However, little is known about the relation between the reduction in synaptic density and the amount of aggregated proteins and therefore we will compare quantitative data on both synaptic density and each hyperphosphorylated tau, amyloid beta and alpha synuclein using tissue microarrays, each covering over 30 brain regions of one individual brain. This study should clarify if the amount of protein aggregates is directly related to the reduction of synaptic density.

 

Tibor Harkany and Julia Marschallinger : Vienna

Identification a novel cell population (TH+/DAT+) in the hypothalamus of post-mortem human tissue.

 The analysis of neurons in mouse hypothalamus based on the single-cell transcriptomics and further clustering analysis has identified some very interesting cell groups. One of them is Tyrosine Hydroxylase (TH)-positive and Dopamine transporter ( DAT)-positive periventricular neurons seen in the hypothalamus, which perhaps are playing a role in circadian rhythms. These are unusual as most of TH cells in the hypothalamus are DAT-negative.

Analysis of neurons in  mouse hypothalamus, based on the single-cell transcriptomics and further clustering analysis have identified some very interesting cell groups. One of them is a TH-positive, DAT-positive periventricular neurons in the hypothalamus, which perhaps play role in circadian rhythms. As opposed to most of TH cells in the hypothalamus which are DAT-negative.In this mouse study the following findings were seen:
Based on transcriptomics data and that neuropeptides are working through specific receptors, neuronal circuits in the hypothalamus were revealed. So identifying the fraction of cell type which expresses the receptor. These cell types which uniquely expressed receptors were found to be a dopaminergic cell type with unique expression of Nmur2 and Nmbr. Further examination of the marker genes concluded that this cell type, in contrast with most of others TH cells in the hypothalamus express DAT and do not express GHRH or Tac1. Additionally this cell type expresses SST (relatively low levels compare to SST clusters), and other markers including Onecut3

Publications