Bio

Amira obtained her Ph.D. in Neuroscience from the KU Leuven, Belgium, in summer 2017. During her doctoral studies, she used clinically valid tests of murine cognition, neuronal plasticity measures in hippocampal and cortical slices, brain lesion methods, pharmacological applications and resting state functional magnetic resonance imaging to characterize the pathophysiology of novel mouse models of Alzheimer’s disease (AD). One of her most gratifying contributions was the development of a new electrophysiology tool to assess synaptopathies, and the establishment of long-term synaptic plasticity from prefrontal cortex of APP knock-in mice. In Autumn 2017, she moved to Dr. Longo’s lab at the Stanford School of Medicine, where she investigates signaling pathways involved in synaptic degeneration. During 3 years of postdoctoral work, she established a multi-electrode array system with eight independent recording chambers that allows high-throughput analyses of multiple long-lasting forms of synaptic plasticity. She also gained experience in RNA-sequencing, molecular biochemistry, signaling mechanisms, target validation and drug development strategies for AD. In October 2020, Amira has been appointed as an Instructor in Neurodegenerative Disease Research, in the Longo lab, to help develop improved and more powerful approaches that will better reveal key synaptic mechanisms and candidate modules associated with neuroplasticity and affected in AD mouse models, by identifying activity-dependent gene expression signatures.

Academic Appointments

Contact

  • Academic
    amiralh@stanford.edu
    University - Other Teaching/Research Department: Adult Neurology Position: Instructor

Additional Info

  • Mail Code: 5489

Links

All Publications

  • Restoring hippocampal glucose metabolism rescues cognition across Alzheimer's disease pathologies. Science (New York, N.Y.) Minhas, P. S., Jones, J. R., Latif-Hernandez, A., Sugiura, Y., Durairaj, A. S., Wang, Q., Mhatre, S. D., Uenaka, T., Crapser, J., Conley, T., Ennerfelt, H., Jung, Y. J., Liu, L., Prasad, P., Jenkins, B. C., Ay, Y. A., Matrongolo, M., Goodman, R., Newmeyer, T., Heard, K., Kang, A., Wilson, E. N., Yang, T., Ullian, E. M., Serrano, G. E., Beach, T. G., Wernig, M., Rabinowitz, J. D., Suematsu, M., Longo, F. M., McReynolds, M. R., Gage, F. H., Andreasson, K. I. 2024; 385 (6711): eabm6131

    Abstract

    Impaired cerebral glucose metabolism is a pathologic feature of Alzheimer's disease (AD), with recent proteomic studies highlighting disrupted glial metabolism in AD. We report that inhibition of indoleamine-2,3-dioxygenase 1 (IDO1), which metabolizes tryptophan to kynurenine (KYN), rescues hippocampal memory function in mouse preclinical models of AD by restoring astrocyte metabolism. Activation of astrocytic IDO1 by amyloid beta and tau oligomers increases KYN and suppresses glycolysis in an aryl hydrocarbon receptor-dependent manner. In amyloid and tau models, IDO1 inhibition improves hippocampal glucose metabolism and rescues hippocampal long-term potentiation in a monocarboxylate transporter-dependent manner. In astrocytic and neuronal cocultures from AD subjects, IDO1 inhibition improved astrocytic production of lactate and uptake by neurons. Thus, IDO1 inhibitors presently developed for cancer might be repurposed for treatment of AD.

    View details for DOI 10.1126/science.abm6131

    View details for PubMedID 39172838

  • A TrkB and TrkC partial agonist restores deficits in synaptic function and promotes activity-dependent synaptic and microglial transcriptomic changes in a late-stage Alzheimer's mouse model. Alzheimer's & dementia : the journal of the Alzheimer's Association Latif-Hernandez, A., Yang, T., Raymond-Butler, R. 3., Losada, P. M., Minhas, P. S., White, H., Tran, K. C., Liu, H., Simmons, D. A., Langness, V., Andreasson, K. I., Wyss-Coray, T., Longo, F. M. 2024

    Abstract

    INTRODUCTION: Tropomyosin related kinase B (TrkB) and C (TrkC) receptor signaling promotes synaptic plasticity and interacts with pathways affected by amyloid beta (Abeta) toxicity. Upregulating TrkB/C signaling could reduce Alzheimer's disease (AD)-related degenerative signaling, memory loss, and synaptic dysfunction.METHODS: PTX-BD10-2 (BD10-2), a small molecule TrkB/C receptor partial agonist, was orally administered to aged London/Swedish-APP mutant mice (APPL/S) and wild-type controls. Effects on memory and hippocampal long-term potentiation (LTP) were assessed using electrophysiology, behavioral studies, immunoblotting, immunofluorescence staining, and RNA sequencing.RESULTS: In APPL/S mice, BD10-2 treatment improved memory and LTP deficits. This was accompanied by normalized phosphorylation of protein kinase B (Akt), calcium-calmodulin-dependent kinase II (CaMKII), and AMPA-type glutamate receptors containing the subunit GluA1; enhanced activity-dependent recruitment of synaptic proteins; and increased excitatory synapse number. BD10-2 also had potentially favorable effects on LTP-dependent complement pathway and synaptic gene transcription.DISCUSSION: BD10-2 prevented APPL/S/Abeta-associated memory and LTP deficits, reduced abnormalities in synapse-related signaling and activity-dependent transcription of synaptic genes, and bolstered transcriptional changes associated with microglial immune response.HIGHLIGHTS: Small molecule modulation of tropomyosin related kinase B (TrkB) and C (TrkC) restores long-term potentiation (LTP) and behavior in an Alzheimer's disease (AD) model. Modulation of TrkB and TrkC regulates synaptic activity-dependent transcription. TrkB and TrkC receptors are candidate targets for translational therapeutics. Electrophysiology combined with transcriptomics elucidates synaptic restoration. LTP identifies neuron and microglia AD-relevant human-mouse co-expression modules.

    View details for DOI 10.1002/alz.13857

    View details for PubMedID 38779814

  • Restoring metabolism of myeloid cells reverses cognitive decline in ageing. Nature Minhas, P. S., Latif-Hernandez, A., McReynolds, M. R., Durairaj, A. S., Wang, Q., Rubin, A., Joshi, A. U., He, J. Q., Gauba, E., Liu, L., Wang, C., Linde, M., Sugiura, Y., Moon, P. K., Majeti, R., Suematsu, M., Mochly-Rosen, D., Weissman, I. L., Longo, F. M., Rabinowitz, J. D., Andreasson, K. I. 2021

    Abstract

    Ageing is characterized by the development of persistent pro-inflammatory responses that contribute to atherosclerosis, metabolic syndrome, cancer and frailty1-3. The ageing brain is also vulnerable to inflammation, as demonstrated by the high prevalence of age-associated cognitive decline and Alzheimer's disease4-6. Systemically, circulating pro-inflammatory factors can promote cognitive decline7,8, and in the brain, microglia lose the ability to clear misfolded proteins that are associated with neurodegeneration9,10. However, the underlying mechanisms that initiate and sustain maladaptive inflammation with ageing are not well defined. Here we show that in ageing mice myeloid cell bioenergetics are suppressed in response to increased signalling by the lipid messenger prostaglandin E2 (PGE2), a major modulator of inflammation11. In ageing macrophages and microglia, PGE2 signalling through its EP2 receptor promotes the sequestration of glucose into glycogen, reducing glucose flux and mitochondrial respiration. This energy-deficient state, which drives maladaptive pro-inflammatory responses, is further augmented by a dependence of aged myeloid cells on glucose as a principal fuel source. In aged mice, inhibition of myeloid EP2 signalling rejuvenates cellular bioenergetics, systemic and brain inflammatory states, hippocampal synaptic plasticity and spatial memory. Moreover, blockade of peripheral myeloid EP2 signalling is sufficient to restore cognition in aged mice. Our study suggests that cognitive ageing is not a static or irrevocable condition but can be reversed by reprogramming myeloid glucose metabolism to restore youthful immune functions.

    View details for DOI 10.1038/s41586-020-03160-0

    View details for PubMedID 33473210

  • The two faces of synaptic failure in AppNL-G-F knock-in mice. Alzheimer's research & therapy Latif-Hernandez, A., Sabanov, V., Ahmed, T., Craessaerts, K., Saito, T., Saido, T., Balschun, D. 2020; 12 (1): 100

    Abstract

    BACKGROUND: Intensive basic and preclinical research into Alzheimer's disease (AD) has yielded important new findings, but they could not yet been translated into effective therapies. One of the reasons is the lack of animal models that sufficiently reproduce the complexity of human AD and the response of human brain circuits to novel treatment approaches. As a step in overcoming these limitations, new App knock-in models have been developed that avoid transgenic APP overexpression and its associated side effects. These mice are proposed to serve as valuable models to examine ASS-related pathology in "preclinical AD."METHODS: Since AD as the most common form of dementia progresses into synaptic failure as a major cause of cognitive deficits, the detailed characterization of synaptic dysfunction in these new models is essential. Here, we addressed this by extracellular and whole-cell patch-clamp recordings in AppNL-G-F mice compared to AppNL animals which served as controls.RESULTS: We found a beginning synaptic impairment (LTP deficit) at 3-4months in the prefrontal cortex of AppNL-G-F mice that is further aggravated and extended to the hippocampus at 6-8months. Measurements of miniature EPSCs and IPSCs point to a marked increase in excitatory and inhibitory presynaptic activity, the latter accompanied by a moderate increase in postsynaptic inhibitory function.CONCLUSIONS: Our data reveal a marked impairment of primarily postsynaptic processes at the level of synaptic plasticity but the dominance of a presumably compensatory presynaptic upregulation at the level of elementary miniature synaptic function.

    View details for DOI 10.1186/s13195-020-00667-6

    View details for PubMedID 32838792

  • Commentary: APP as a Mediator of the Synapse Pathology in Alzheimer's Disease. Frontiers in cellular neuroscience Schreurs, A., Latif-Hernandez, A., Uwineza, A. 2018; 12: 150

    View details for DOI 10.3389/fncel.2018.00150

    View details for PubMedID 29905239

    View details for PubMedCentralID PMC5990595