Mechanisms of Memory and Alzheimer’s Disease Pathogenesis
At the conceptual level the “Mechanisms of memory and Alzheimer’s disease pathogenesis” research team will work on the mechanisms underlying learning and memory, and in different conditions that lead to neurodegeneration, with a focus on Alzheimer’s disease pathogenesis.
At the technical level, this is a multidisciplinary team, with expertise in biochemical, cellular imaging, animal behavior, electrophysiology and brain MRI methodologies; and experience in cell culture, animal models and human cohorts. Therefore, our goal is to tackle scientific questions with the most adequate technical approach, joining efforts with different disciplines.
The research team will work around projects addressing research lines within the scope of learning and memory and neurodegenerative disorders that impact cognition:
1. Synaptic plasticity regulation along the longitudinal hippocampal axis.
The main goal of this project is to understand how different subdivisions of the hippocampus, along its longitudinal axis, from dorsal to ventral in rodents, contribute to differential components of spatial memory.
2. Lipids in learning and memory.
Here, we will study how lipid signaling affects learning and memory. Based on lipidomic signatures, we are focusing on the impact of the phospholipase D (PLD) pathway on behaviors that rely on the longitudinal hippocampal axis.
3. Lipids in Alzheimer’s disease and associated neurodegenerative disorders.
In this project we are following our long standing work using lipidomics to unravel signatures that highlight the role of lipid signaling in Alzheimer’s disease and other neurodegenerative disorders.
4. Sleep, Synaptic plasticity and Alzheimer’s disease.
Sleep has been shown to be fundamental for synaptic plasticity and sleep dysregulation has been implicated in Alzheimer’s disease pathogenesis. Here, we will explore the mechanistic links between these associations.
5. Brain Imaging in Alzheimer’s disease and associated neurodegenerative disorders.
Our team has a strong background in clinical neuroimaging and here we use two main approaches: studying cohorts that have both neuropathology and brain MRI data; and developing new MRI-based segmentation algorithms.
6. Brain Imaging in cognition.
Here, we will use MRI-based approaches to question and challenge the roles of the hippocampus in different conditions, targeting social memory and spatial information.
We have developed a multidisciplinary environment, which is unique for training scientists to acquire various research skills that can be applied to basic and clinical research. Moreover, in the last few years our research team has published in reference journals (such as Cell Reports, Journal of Neuroscience or The New England Journal of Medicine), acquired competitive funding (from the Portuguese Foundation for Science and Technology, Brain and Behavior Research Foundation, European Commission or BIAL Foundation) and trained various Master and PhD students with backgrounds in medicine, biology, biochemistry or biomedical engineering.
Selected Research Outputs
1. Divergent MRI atrophy patterns in Alzheimer’s disease and primary age-related tauopathy. Quintas-Neves M, Teylan MA, Morais-Ribeiro R, Almeida F, Mock CN, Kukull WA, Crary JF, Oliveira TG. Neurobiology of Aging. 2022 May 1;117:1-11. doi: 10.1016/j.neurobiolaging.2022.04.013.
2. Effects of APOE4 allelic dosage on lipidomic signatures in the entorhinal cortex of aged mice. Miranda AM, Ashok A, Chan RB, Zhou B, Xu Y, McIntire LB, Area-Gomez E, Di Paolo G, Duff KE, Oliveira TG*, Tal Nuriel*. Transl Psychiatry. 2022 Mar 29;12(1):129. doi: 10.1038/s41398-022-01881-6.
3. Autosomal Dominant Osteopetrosis. Meira T, Soares-Fernandes JP. N Engl J Med. 2022 Sep 29;387(13):e27. doi: 10.1056/NEJMicm2202055.
4. Medial Entorhinal Cortex Excitatory Neurons Are Necessary for Accurate Timing. Dias M, Ferreira R, Remondes M. J Neurosci. 2021 Dec 1;41(48):9932-9943.
5. Phospholipase D1 Ablation Disrupts Mouse Longitudinal Hippocampal Axis Organization and Functioning. Santa-Marinha L, Castanho I, Silva RR, Bravo FV, Miranda AM, Meira T, Morais-Ribeiro R, Marques F, Xu Y, Point du Jour K, Wenk M, Chan RB, Di Paolo G, Pinto V, Oliveira TG. Cell Rep. 2020 Mar 24;30(12):4197-4208.e6.
6. Magnetic resonance imaging brain atrophy assessment in primary age-related tauopathy (PART). Quintas-Neves M, Teylan MA, Besser L, Soares-Fernandes J, Mock CN, Kukull WA, Crary JF, Oliveira TG. Acta Neuropathol Commun. 2019 Dec 9;7(1):204.
7. Differential lipid composition and regulation along the hippocampal longitudinal axis. Miranda AM, Bravo FV, Chan RB, Sousa N, Di Paolo G, Oliveira TG. Transl Psychiatry. 2019 Apr 26;9(1):144.
8. Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures. Miranda AM, Lasiecka ZM, Xu Y, Neufeld J, Shahriar S, Simoes S, Chan RB, Oliveira TG, Small SA, Di Paolo G. Nat Commun. 2018 Jan 18;9(1):291.
9. A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics. Meira T, Leroy F, Buss EW, Oliva A, Park J, Siegelbaum SA. Nat Commun. 2018 Oct 9;9(1):4163.
10. Loss of Bin1 Promotes the Propagation of Tau Pathology. Calafate S, Flavin W, Verstreken P, Moechars D. Cell Rep. 2016 Oct 18;17(4):931-940. doi: 10.1016/j.celrep.2016.09.063.