Dr. Tariq Ahmed



Tel: +974 44546432
Dr. Tariq Ahmed attained a BSc (Hons) in Biochemistry (Liverpool University) and an MSc in Neuroscience (Aberdeen University).Then was awarded a PhD in Yeast Molecular Biology from the University of Manchester Institute of Science and Technology (UMIST, UK) in 1995. After working for Kicho Laboratories in Liverpool (UK), He moved in 1997 to the Leibniz-Institute of Neurobiology in Magdeburg (Germany). In 2002 I relocated to the Thomas H Christopher Parkinson’s Laboratories, Sun Health Research Institute, Sun City, Arizona (USA) as Principal Scientist. For the last 8 years, Dr. Ahmed have been a Senior Research Scientist within the Lab of Biological Psychology at the KU Leuven, Belgium.
The hippocampus is a brain structure that is required for learning and memory. The underlying mechanisms for cognition are thought to be the result of changes in synaptic potentials within principal neurones. Ageing and many neurological disorders, including many forms of dementia, manifest initially as mild cognitive deficits in humans, which proceed into severe memory impairment; seen as lesions post-mortem. Synaptic plasticity (changes in membrane potentials at synapses) predominantly long-term potentiation (LTP); and with newer evidence that long term depression, (LTD), are accepted as the paramount tools to explore changes in cellular forms of learning and memory formation. Late forms of hippocampal synaptic plasticity (> 4 hour), share many of the molecular and cellular mechanisms associated with learning and memory. Which include the molecular processes of translation and transcription, mediated by signal transduction pathways. Interestingly, a vast majority of neuro-psychiatric disorders can be classified as synaptopathies. A common characteristic of these synaptopathies has been the dysequilibria in kinase and phosphatase activity, which results in, initially synaptic dystrophy. Examples of the kinases include the serine/ threonine and non-receptor Src-family tyrosine (SFK) kinases which all effect GSK3β activity; a prominent metabolic sensor kinase.
Natural ageing is generally accompanied by a decline of cognitive faculties, such as learning, memory and executive control. This can result in reduction in the quality of life of the individual and places increased socio-economic burden on society. With the substantially increased life expectancy in many countries due to improved healthcare facilities, the incidence of age-related disorders is increasing at an exceptional rate. In this context, dementia and Alzheimer’s disease (AD) are two of the most frequently diagnosed neurodegenerative disorders leading to a loss of cognitive functions in some cases within a decade; challenging health care systems in industrialized and developing nations. An example of this challenge is the necessity of palliative care 24/7 in later AD stages, which greatly stresses health care budgets. Therefore, disease slowing or curing medications not only for AD, but for other neurological disorders, are an urgent necessity. Early investigations into the cause of these ageing effects, pointed to an extensive age-related loss of neurones in the prefrontal cortex and in medial temporal lobe structures such as the hippocampus and amygdala. However, more refined morphological and electrophysiological approaches have identified that in the hippocampus ageing was accompanied by a decrease in functional synapses and not necessarily neuronal loss. This is in good agreement with findings that different neurocognitive and neurodegenerative disorders converge mechanistically at synaptic dysfunctions: synaptopathies. Many of these synaptopathies have been found to have dysequilibria in kinase and phosphatase activity within synapses/ neurones, which results in the initial synaptic dystrophy. In Alzheimer’s disease (AD) for example, one hypothesis is that synaptotoxic oligomeric species bind to the prion PrPC receptor and via Fyn facilitates hyperphosphorylation of the microtubule associated protein Tau at multiple sites expediting its mis-localisation from the soma to dendrites where it effects pathology. Examples of the kinases involved in Tau phosphorylation include the serine/threonine kinases (PI3K; PKC; MARK; MAPK) and non-receptor Src-family tyrosine (SFK) kinases (Pyk1, Fyn and Src) which all effect GSK3β activity; a prominent metabolic sensor kinase and arguably the major Tau kinase which has been found to be associated with tangles. Many of these enzymes are required for physiological functioning and are implicated in cellular models of learning and memory: long-term potentiation (LTP) and long-term depression (LTD) which represent the two most established models. N-methyl-D-aspartate (NMDA) receptor mediated forms of LTP and LTD are considered as prime cellular models of Hebbian learning and memory and share many of the molecular mechanisms and signalling pathways involved in learning and memory. Whereas the role of kinases in LTP and learning and memory have been extensively studied, little attention has been paid to enzymes involved in LTD. Recent evidence indicates that LTD may be required for certain hippocampus-dependent learning processes and neuronal flexibility. For LTD, GSK3β and the protein phosphatases: PP1, PP2A and PP2B have been identified as being necessary. Most notably all of these signalling mechanisms including those involved in LTP/ LTD and cognition, affect the trafficking of the ionotropic glutamate receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPAR) to the plasma membrane. Importantly, LTP was reported by several authors to be subject to age-dependent changes. In a recent report (Trovo et al. 2013) we demonstrated that the loss of myristoylated alanine-rich C kinase substrate (MARCKS) in the hippocampus of old mice results in impaired LTP and cognition. More recently we have demonstrated that cholesterol loss (approx. 25%) from neuronal membranes with age impairs synaptic plasticity and cognition; again by affecting AMPAR receptor trafficking all due to high PI3K activity. Not surprisingly overactive GSK3β and loss of PP2A has been reported to be at the centre of tauopathies. We have recently identified that GSK3β is required for both LTP and LTD using GSK3β neural specific KO mice (Ahmed et al submitted). Further, we documented that in a Tau model the increased GSK3β kinase activity resulted in impaired LTD and was rescued by inhibition of GSK3 (with antagonists) and application of selenate a PP2A agonist (Ahmed et al submitted). Unsurprisingly, these two protein are closely associated with amino-terminal of the 2N-4R Tau protein making them both prime targets for therapeutic studies in AD. PP2A is the major phosphatase in neuronal cells (genetic ablation is lethal) and its dysequilibrium results in many neuronal dysfunctions, including intellectual disability and AD. Neuronal specific PP2A-holoenzyme (compromised of the catalytic subunit, PP2Ac-36 KDa; regulatory and binding subunits PR55B-52 KDa and PR61B (either αβɛ): 52, 52 and 55 KDa respectively) is tightly regulated by phosphorylation and methylation. Phosphorylation by multiple kinases (e.g., PKA, MAPK), at Tyr307 inhibits the recruitment of the PR55B and PR61B αβɛ (isotypes) family members to the core enzyme and association with Tau. PP2A is also regulated by methylation at Leu309 of the catalytic subunit, by Leucine carboxyl methyltransferase 1 (LCMT1) which was found to be required only for the binding of certain regulatory B subunits and results in enhanced catalytic activity. The methylation of the C-terminal tail can be reversed by the specific phosphatase methylesterase (PME1). The latter two enzymes have also been found to be dysregulated in AD and tauopathies, indicating a pivotal role in the disease pathology. The goal of our group is to study GSK3β and PP2A holozyme in different neurone types and asses how alterations affect synaptic and neuronal plasticity as use these molecules for therapeutic development in neurological disorders.
Marschner L, Schreurs A, Lechat B, Mogensen J, Roebroek A, Ahmed T, Balschun D (2018). Single mild traumatic brain injury results in transient deficits in spatial long-term memory and altered search strategies. Behavioural Brain Res. In press

Salas I, Weerasekera A, Ahmed T, Callaerts-Vegh Z, Himmelreich U, D'Hooge R, Balschun D, Saido TC, de Strooper B, Dotti CG (2018). High fat diet treatment impairs hippocampal long-term potentiation without alterations of the core neuropathological features of Alzheimer disease. Neurobiology of Dis. In press

Marciniak E, Leboucher A, Caron E, Ahmed T*, Tailleux A, Dumont J, Issad T, Gerhardt E, Pagesy P, Vileno M, Bournonville C, Hamdane M, Bantubungi K, Lancel S, Demeyer D, Eddarkaoui S, Vallez E, Vieau D, Humez S, Faivre E, Grenier-Boley Outeiro TF, Staels B, Amouyel P, Balschun B, Buee L, Blum D (2017). Tau deletion promotes brain insulin resistance. J Exp Med. 214:2257-2269. doi: 10.1084/jem.20161731.

Collaborator Name Institute Research Area
van Leuven
KU Leuven, Belgium Alzheimer’s disease (AD): Tauopathy (P301L, BiAT, BiGT); GSK3β KO, GSK3βS9A, Tg mice models.
De Strooper
KU leuven, Belgium APP/PS1 and APP/PS1 “knock in” mice models.
Luc Buee INSERM, University Lille, France Tau KO and (Tau 22) a Tauopathy mouse models.
David Blum INSERM, University Lille, France Tau KO and (Tau 22) a Tauopathy mouse models.
Valerie Vingtdeux INSERM, University Lille, France αAMPK1/2 mouse model of ageing and AD
Claudia Bagnia KU Leuven, Belgium Fragile X, Cyfip1 mouse models of autism
Carlos Dotti KU Leuven, Belgium/
Cajal Institute Madrid, Spain.
Ageing models/ Type 2 Diabetes (high fat diet) APO/Clu J mouse models.
Brigitta Qualmann University Jena,
Syndapin 1 and ABP1 KO mouse models.
Name Institution Period
Gergios Kogias 2015-2016
An Schreurs 2014-2018
Linda Marschner 2013-2016
Marta Carmen Bovet 2013-2018
Amira Latif-Hernandez 2013-2017
Tim Tambuyzer 2012-2017
Ann Van Der Jeugd 2009-2014
Enrico Faldini 2007-2012
Jaideep Kershavan 2004-2005
Steven Presgraves 2001-2004

I have, in the last 20 years, supervised over 20 Master/ Bachelors students in all aspects of electrophysiology and molecular biology.
QBRI Start-up grant: (VR10). Protein phosphatase 2A (PP2A) as an alternative therapeutic target for Alzheimer’s disease and other neurological disorders.

FWO (Belgian National Government Grant) G0A1414N (01/01/2014 - 31/12/2017). Vennekens R and Ahmed T. The role of the TRPM4 ion channel in a long-term synaptic potentiation and memory formation.

FWO (Belgian National Government Grant) G046910N (01/01/2010 - 31/12/2013). Legius E, Balschun D and Ahmed T: Characterization and treatment of cognitive deficits in Spred1 knockout mice and in patients with Legius syndrome and neurofibromatosis type 1.
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