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- Telephone: +44 (0) 191 208 1225
- Address: Institute of Neuroscience
Ageing Research Laboratories
Campus for Ageing and Vitality
Newcastle upon Tyne, NE4 5PL
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.
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
- Unger MS, Marschallinger J, Kaindl J, Klein B, Johnson M, Khundakar AA, Roßner S, Heneka MT, Couillard-Despres S, Rockenstein D, Masliah E, Attems J, Aigner L. Doublecortin expression in CD8+ T-cells and microglia at sites of amyloid-β plaques: A potential role in shaping plaque pathology?. Alzheimer's & Dementia 2018, Epub ahead of print.
- McAleese KE, Walker L, Graham S, Moya ELJ, Johnson M, Erskine D, Colloby SJ, Dey M, Martin-Ruiz C, Taylor J-P, Thomas AJ, McKeith IG, De Carli C, Attems J. Parietal white matter lesions in Alzheimer's disease are associated with cortical neurodegenerative pathology, but not with small vessel disease. Acta Neuropathologica 2017, ePub ahead of print.
- Walker L, McAleese KE, Johnson M, Khundakar AA, Erskine D, Thomas AJ, McKeith IG, Attems J. Quantitative neuropathology: an update on automated methodologies and implicationsfor large scale cohorts. Journal of Neural Transmission 2017, (ePub ahead of Print).
- Vallortigara J, Whitfield D, Quelch W, Alghamdi A, Howlett D, Hortobágyi T, Johnson M, Attems J, O'Brien JT, Thomas A, Ballard CG, Aarsland D, Francis PT. Decreased Levels of VAMP2 and Monomeric Alpha-Synuclein Correlate with Duration of Dementia. Journal of Alzheimer's Disease 2016, 50(1), 101-110.
- Walker L, Thomas A, Lett DJ, McAleese KE, Johnson M, Attems J. Investigating the pathological correlate of motor dysfunction in DLB and PDD. In: 117th meeting of the British Neuropathological Society. 2016, London: Wiley-Blackwell Publishing Ltd.
- Manousopoulou A, Gatherer M, Smith C, Nicoll JAR, Woelk CH, Johnson M, Kalaria R, Attems J, Garbis SD, Carare RO. Systems proteomic analysis reveals that clusterin and tissue inhibitor of metalloproteinases 3 increase in leptomeningeal arteries affected by cerebral amyloid angiopathy. Neuropathology and Applied Neurobiology 2016, (ePub ahead of Print).
- Walker L, McAleese KE, Thomas AJ, Johnson M, Martin-Ruiz C, Parker C, Colloby SJ, Jellinger K, Attems J. Neuropathologically mixed Alzheimer's and Lewy body disease: burden of pathological protein aggregates differs between clinical phenotypes. Acta Neuropathologica 2015, 129(5), 729-748.
- Whitfield DR, Vallortigara J, Alghamdi A, Howlett D, Hortobagyi T, Johnson M, Attems J, Newhouse S, Ballard C, Thomas AJ, O'Brien JT, Aarsland D, Francis PT. Assessment of ZnT3 and PSD95 protein levels in Lewy body dementias and Alzheimer's disease: association with cognitive impairment. Neurobiology of Aging 2014, 35(12), 2836-2844.
- Vallortigara J, Rangarajan S, Whitfield D, Alghamdi A, Howlett D, Hortobagyi T, Johnson M, Attems J, Ballard C, Thomas A, O'Brien J, Aarsland D, Francis P. Dynamin1 concentration in the prefrontal cortex is associated with cognitive impairment in Lewy body dementia. F1000Research 2014, 3, 108.
- Johnson M, Perry EK, Baker C, Attems J. Neurogenic marker alterations in the hippocampus in relation to cholinergic therapy in Lewy Body dementia. In: Proceedings of the 115th Meeting of the British Neuropathological Society. 2014, London: Wiley-Blackwell.
- McParland S, McAleese K, Walker L, Johnson M, Fielder E, Knowles I, Attems J. Tissue microarray in the quantification of hyper-phosphorylated tau, amyloid-beta and alpha-synuclein. In: 114th Meeting of the British Neuropathological Society. 2013, London: Wiley-Blackwell Publishing Ltd.
- Ekonomou A, Johnson M, Perry RH, Perry EK, Kalaria RN, Minger SL, Ballard CG. Increased neural progenitors in individuals with cerebral small vessel disease. Neuropathology and Applied Neurobiology 2012, 38(4), 344-353.
- McAleese KE, Firbank M, Johnson M, Walker L, Hunter D, Sun L, Hall R, O'Brien JT, Attems J. Magnetic resonance imaging detects subcortical vascular pathology in post mortem brains. In: 113th Meeting of the British Neuropathological Society. 2012, London, UK.
- Perry EK, Johnson M, Ekonomou A, Perry RH, Ballard C, Attems J. Neurogenic abnormalities in Alzheimer's disease differ between stages of neurogenesis and are partly related to cholinergic pathology. Neurobiology of Disease 2012, 47(2), 155-162.
- Johnson M, Ekonomou A, Hobbs C, Ballard CG, Perry RH, Perry EK. Neurogenic Marker Abnormalities in the Hippocampus in Dementia with Lewy Bodies. Hippocampus 2011, 21(10), 1126-1136.
- Bernstein HG, Johnson M, Perry RH, LeBeau FEN, Dobrowolny H, Bogerts B, Perry EK. Partial loss of parvalbumin-containing hippocampal interneurons in dementia with Lewy bodies. Neuropathology 2011, 31(1), 1-10.
- Ziabreva I, Ballard C, Johnson M, Larsen JP, McKeith I, Perry R, Aarsland D, Perry E. Loss of Musashi1 in Lewy body dementia associated with cholinergic deficit. Neuropathology and Applied Neurobiology 2007, 33(5), 586-590.
- Perry EK, Piggott MA, Court JA, Johnson M, Perry RH. Transmitters in the Developing and Senescent Human Brain. Annals of the New York Academy of Sciences 2006, 695(1), 69-72.
- Court JA, Johnson M, Religa D, Keverne J, Kalaria R, Jaros E, McKeith IG, Perry R, Naslund J, Perry EK. Attenuation of A beta deposition in the entorhinal cortex of normal elderly individuals associated with tobacco smoking. Neuropathology and Applied Neurobiology 2005, 31(5), 522-535.
- Teaktong T, Graham AJ, Court JA, Perry RH, Jaros E, Johnson M, Hall R, Perry EK. Nicotinic acetylcholine receptor immunohistochemistry in Alzheimer's disease and dementia with Lewy bodies: differential neuronal and astroglial pathology. Journal of the Neurological Sciences 2004, 225(1-2), 39-49.
- Teaktong T, Graham AJ, Johnson M, Court JA, Perry EK. Selective changes in nicotinic acetylcholine receptor subtypes related to tobacco smoking: an immunohistochemical study. Neuropathology and Applied Neurobiology 2004, 30(3), 243-254.
- Teaktong T, Graham A, Court J, Perry R, Jaros E, Johnson M, Hall R, Perry E. Alzheimer's disease is associated with a selective increase in alpha 7 nicotinic acetylcholine receptor immunoreactivity in astrocytes. Glia 2003, 41(2), 207-211.
- Perry EK, Piggott MA, Johnson M, Ballard CG, McKeith IG, Jaros E, Perry RH. Cholinergic and monoaminergic correlates of clinical symptoms in dementia with Lewy bodies. In: Mapping the Progress of Alzheimer's and Parkinson's Disease. 2002, Kyoto, Japan: Springer.
- Perry EK, Piggott MA, Johnson M, Ballard CG, McKeith IG, Burn DJ. Neurotransmitter correlates of neuropsychiatric symptoms in dementia with Lewy bodies. In: Bédard, M.-A, ed. Mental & Behavioural Dysfunction in Movement Disorders. Totowa, New Jersey, USA: Humana Press Inc, 2002, pp.285-294.
- Bednar I, Hellstrom-Lindahl E, Mousavi M, Nordberg A, Lee M, Johnson M, Hal R, Perry E, Court J. Nicotine treatment attenuates beta-amyloidosis in brain of transgenic APPsw mice. In: Neurobiology of Aging. 2002, Elsevier Inc.
- Teaktong T, Graham A, Court J, Johnson M, Hall R, Perry E, Perry R, Jaros E. Nicotinic acetylcholine receptor immunohistochemistry in Alzheimer's disease and dementia with Lewy bodies: Increased alpha 7 immunoreactivity of astrocytes in Alzheimer's disease. In: Neurobiology of Aging. 2002, Elsevier Inc.
- Johnson M, Court J, Perry E, Kalaria R, McKeith I, Jaros E, Perry R, Naslund J, Religa D. Tobacco use is associated with attenuation of beta-amyloidosis in hippocampus and entorhinal cortex of normal elderly individuals. In: Neurobiology of Aging. 2002, Elsevier Inc.
- Svedberg MM, Svensson AL, Johnson M, Lee M, Cohen O, Court J, Soreq H, Perry E, Nordberg A. Upregulation of neuronal nicotinic receptor subunits alpha 4, beta 2, and alpha 7 in transgenic mice overexpressing human acetylcholinesterase. Journal of Molecular Neuroscience 2002, 18(3), 211-222.
- Marutle A, Zhang X, Court J, Piggott M, Johnson M, Perry R, Perry E, Nordberg A. Laminar distribution of nicotinic receptor subtypes in cortical regions in schizophrenia. Journal of Chemical Neuroanatomy 2001, 22(1-2), 115-126.
- Court JA, Ballard CG, Piggott MA, Johnson M, O'Brien JT, Holmes C, Cairns N, Lantos P, Perry RH, Jaros E, Perry EK. Visual hallucinations are associated with lower αbungarotoxin binding in dementia with Lewy bodies. Pharmacology Biochemistry and Behavior 2001, 70(4), 571-579.
- Piggott MA, Marshall EF, Thomas N, Lloyd S, Court JA, Jaros E, Burn D, Johnson M, Perry RH, McKeith IG, Ballard C, Perry EK. Striatal dopaminergic markers in dementia with Lewy bodies, Alzheimer's and Parkinson's diseases: rostrocaudal distribution. Brain 1999, 122(8), 1449-1468.
- Perry EK, Ballard C, Spurden D, Cheng A, Johnson M, McKeith I, Piggott M, Perry R. Cholinergic systems in the human brain: psychopharmacology and psychosis. Alzheimers' Disease Review 1998, 3, 117-124.
- Perry E, Court J, Goodchild R, Griffiths M, Jaros E, Johnson M, Lloyd S, Piggott M, Spurden D, Ballard C, McKeith I, Perry R. Clinical neurochemistry: developments in dementia research based on brain bank material. Journal of Neural Transmission 1998, 105(8-9), 915-933.
- Piggott MA, Perry EK, Marshall EF, McKeith IG, Johnson M, Melrose HL, Court JA, Lloyd S, Fairbairn A, Brown A, Thompson P, Perry RH. Nigrostriatal dopaminergic activities in dementia with Lewy bodies in relation to neuroleptic sensitivity: Comparisons with Parkinson's disease. Biological Psychiatry 1998, 44(8), 765-774.
- Piggott MA, Court JA, Perry EK, Lloyd S, Thomas NJ, Smith ZM, Johnson M, Perry RH, McKeith IG. Dopaminergic and nicotinic interactions in the human striatum in dementia with Lewy bodies, chronic schizophrenia and Parkinson's disease. European Neuropsychopharmacology 1996, 6(4), 103-104.
- Johnson M, Perry RH, Piggott MA, Court JA, Spurden D, Lloyd S, Ince PG, Perry EK. Glutamate receptor binding in the human hippocampus and adjacent cortex during development and aging. Neurobiology of Aging 1996, 17(4), 639-651.
- Johnson M, Perry EK, Ince PG, Shaw PJ, Perry RH. Autoradiographic comparison of the distribution of [3H]MK801 and [3H]CNQX in the human cerebellum during development and aging. Brain Research 1993, 615(2), 259-266.
- Kerwin JM, Morris CM, Johnson M, Perry RH, Perry EK. Hippocampal p75 Nerve Growth Factor Receptor Immunoreactivity in Development, Normal Aging and Senescence. Acta Anatomica 1993, 147(4), 216-222.
- Court JA, Perry EK, Johnson M, Piggott MA, Kerwin JA, Perry RH, Ince PG. Regional patterns of cholinergic and glutamate activity in the developing and aging human brain. Developmental Brain Research 1993, 74(1), 73-82.
- Perry EK, Piggott MA, Court JA, Johnson M, Perry RH. Transmitters in the Developing and Senescent Human Brain. In: Alzheimer's Disease: Amyloid Precursor Proteins, Signal Transduction, and Neuronal Transplantation. 1993.
- Perry EK, Court JA, Johnson M, Piggott MA, Perry RH. Autoradiographic distribution of [3H]nicotine binding in human cortex: Relative abundance in subicular complex. Journal of Chemical Neuroanatomy 1992, 5(5), 399-405.
- Johnson M, Perry RH, Charlton FG, Moses MA, Court JA, Perry EK. Distribution of [3H]MK801 binding in the normal aged human hippocampus. Brain Research 1989, 499(1), 184-187.
- Perry EK, Smith CJ, Perry RH, Johnson M, Fairbairn AF. Nicotinic (3H nicotine) receptor binding in human brain: characterization and involvement in cholinergic neuropathology. Neuroscience Research Communications 1989, 5(2), 117-124.
- Perry EK, Smith CJ, Perry RH, Whitford C, Johnson M, Birdsall NJ. Regional distribution of muscarinic and nicotinic cholinergic receptor binding activities in the human brain. Journal of Chemical Neuroanatomy 1989, 2(4), 189-199.
- Perry EK, Smith CJ, Atack JR, Candy JM, Johnson M, Perry RH. Neocortical Cholinergic Enzyme and Receptor Activities in the Human Fetal Brain. Journal of Neurochemistry 1986, 47(4), 1262-1269.
- SMITH CJ, PERRY EK, PERRY RH, JOHNSON M, CANDY J. THE STATUS OF HIPPOCAMPAL CHOLINERGIC RECEPTORS IN HUMAN COGNITIVE DISORDERS. In: BIOCHEMICAL SOCIETY TRANSACTIONS. 1986.
- Candy JM, Perry EK, Perry RH, Bloxham CA, Thompson J, Johnson M, Oakley AE, Edwardson JA. Evidence for the early prenatal development of cortical cholinergic afferents from the nucleus of Meynert in the human foetus. Neuroscience Letters 1985, 61(1-2), 91-95.