Dr Lauren Walker
- Email: firstname.lastname@example.org
- Telephone: +44 (0) 191 208 1213
- Fax: +44 (0) 191 208 1101
- Address: Ageing Reseach Laboratories
Institute of Neuroscience
Campus for Ageing and Health
I am a post-doctoral research associate in the lab of Prof. Johannes Attems, and my current research interests lie in investigating the effects of multiple pathological lesions on clinical phenotype in neurodegenerative disorders (e.g. Alzheimer's disease and Lewy body disease). Using a quantitative clinico-patholigical approach we aim to tease is distinct clinico-pathologcal phenotypes which may ultimately lead to tailored treatment options for patients.
Neurodegenerative Pathology Research Group website:
PhD Neurodegenerative Pathology - Newcastle University
MRes Medical and Molecular Bioscience - Newcastle University
BSc (Hons) Physiological Science - Newcastle University
British Neuropathological Society
Recent data has suggested a subspecies of Aβ, termed ‘pyroglutamylated Aβ’ (pAβ), may play a crucial role in pathology. pAβ is more abundant in AD and is cytotoxic in the presence of hyperphosphorylated tau (HP-T). pAβ expression also correlates with the presence of HP-T and clinical dementia.
To further investigate the role of pAβ in AD and LBD we are currently using brain tissue from the Newcastle Brain Tissue Resource to quantitatively assess pAβ, HP-T and α-syn, and will compare the results with clinical findings. Using immunohistochemical and biochemical techniques we aim to correlate pAβ with neurofibrillary tangle development, and assess its potential role in synaptic injury and inflammatory response. In addition, we will compare pAβ expression in cerebrospinal fluid (CSF) with parenchymal deposits in the brain. The results will clarify if pAβ plays a crucial role in the pathogenesis of both AD and LBD. If so, pAβ may represent a potential biomarker in CSF and imaging diagnostics, and therapeutic target.
High throughput tissue microarray
Tissue microarray (TMA) is a technique most commonly employed in tumour studies, involving the extraction and transfer of a large number of samples into a single block, allowing high throughput analysis. This technique has previously been adapted to investigate white matter disease in human brain tissue, highlighting its potential use in dementia research. Our laboratory has developed a protocol to analyse 15 anatomically-distinct cortical and sub-cortical brain regions on one slide. Using an automated microscope and image analysis system we have accurately quantified a number of neuropathological lesions in human post-mortem brains from the Newcastle Brain Tissue Resource. Current analysis of over 150 cases has demonstrated a large variation of pathology load in patients with severe neurodegenerative diseases, which has not been appreciated using internationally recognised semi-quantitative staging criteria. This ongoing project will provide important information that can be used in clinico-pathological studies to assess the effect of single and multiple pathologies, on cognitive status.
TDP-43 in cerebral multi-morbidity
TDP-43 is the characteristic pathology of some types of motor neuron disease and frontal temporal dementia. However, recent studies have demonstrated TDP-43 is also found in Alzheimer's disease, where it follows a distinct topographic sequence of progression (Joseph et al, 2014; 2016). Using tissue from the Newcastle Brain Tissue Resource, we are currently investigating TDP-43 expression in other age-related neurodegenerative disorders.
TeachingAssisted supervision of postgraduate and undergraduate research students
- 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).
- Longmoor GK, Lange CH, Darvell H, Walker L, Rytkönen S, Vatka E, Hohtola E, Orell M, Smulders TV. Different seasonal patterns in song system volume in willow tits and great tits. Brain, Behavior and Evolution 2016, 87(4), 265-274.
- Mcaleese KE, Walker L, Erskine D, Thomas AJ, Mckeith IG, Attems J. TDP-43 pathology in Alzheimer's disease, dementia with Lewy bodies and ageing. Brain Pathology 2016, (ePub ahead of Print).
- Tiraboschi P, Attems J, Thomas A, Brown A, Jaros E, Lett DJ, Ossola M, Perry RH, Ramsay L, Walker L, McKeith IG. Clinicians' ability to diagnose dementia with Lewy bodies is not affected by β Normal 0 false false false EN-GB X-NONE X-NONE -amyloid load. Neurology 2015, 84(5), 496-499.
- 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.
- McAleese K, Firbank M, Dey M, Colloby SJ, Walker L, Johnson M, Beverley JR, Taylor JP, Thomas AJ, O'Brien JT, Attems J. Cortical tau load is associated with white matter hyperintensities. Acta Neuropathologica Communications 2015, 3, 60.
- Thal DR, von Arnim CAF, Griffin WST, Mrak RE, Walker L, Attems J, Arzberger T. Frontotemporal lobar degeneration FTLD-tau: preclinical lesions, vascular, and Alzheimer-related co-pathologies. Journal of Neural Transmission 2015, 122(7), 1007-1018.
- Attems J, Walker L, Jellinger KA. Olfaction and Aging: A Mini-Review. Gerontology 2015, 61(6), 485-490.
- Mandler M, Walker L, Santic R, Hanson P, Upadhaya AR, Colloby SJ, Morris CM, Thal DR, Thomas AJ, Schneeberger A, Attems J. Pyroglutamylated amyloid-β is associated with hyperphosphorylated tau and severity of Alzheimer’s disease. Acta Neuropathologica 2014, 128, 67-79.
- Attems J, Walker L, Jellinger KA. Olfactory bulb involvement in neurodegenerative diseases. Acta Neuropathologica 2014, 127(4), 459-475.
- Clowry GJ, Walker L, Davies P. The effects of botulinum neurotoxin A induced muscle paresis during a critical period upon muscle and spinal cord development in the rat. Experimental Neurology 2006, 202(2), 456-469.
- 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.
- McAleese KE, Walker L, Erskine D, Attems J. The prevalence of TDP-43 pathology in Alzheimer's disease, Lewy body dementia and mixed Alzheimer's disease and Lewy body disease. In: 17th meeting of the British Neuropathological Society. 2016, London, UK: Wiley-Blackwell.
- Attems J, Walker L, Santic R, Upadhaya AR, Colloby S, Thal D, Thomas A, Schneeberger A, Mandler M. Pyroglutamylated Amyloid-beta correlates with Hyperphosphorylated Tau and Severity of Alzheimer's Disease. In: American Association of Neuropathologists, Inc. 90th Annual Meeting. 2014, Portland, OR, USA: Lippincott Williams & Wilkins, Ltd.
- Walker L, Thomas AJ, Attems J. Quantification of pathological lesions detects clinico-pathological phenotypes of mixed AD/LBD. In: BRAIN PATHOLOGY. 2014, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA: 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.
- 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.