La Fundación CIEN en la AAIC 2017

• Location N11-B. F3-07
• Tue, Jul 18 (4:15pm - 5:45pm)
• Session chair(s): Jesus Avila, Khalid Iqbal

2016 has marked the 30th anniversary of the seminal discovery reported almost simultaneously by several laboratories in Europe, Japan and the US identifying tau protein as the main component paired helical filaments in the neurofibrillary tanglespresent in the brain of AD patients. Misfolded, hyperphosphorylated, silver-stain-negative tau accumulates first in the locus coeruleus, stereotypically spreading later to the entorhinal cortex and then the hippocampus and neocortex. Increasing evidence have shown the existence of diverse conformational tau strains and a nucleation-dependent aggregation mechanism followed by seed-dependent cell-to-cell propagation of the pathology, reminiscent of a prion-like mechanism. Clinical symptoms would only manifest after extensive propagation and arresting the tau spreading at a preclinical stage might therefore prevent the appearance of clinical symptoms. Thus, removing extracellular tau species by passive or active immunotherapy constitutes a potential mechanism-based therapy that is already being pursued in preclinical models and in early clinical trials. Despite the remarkable advances made in recent years in understanding tau pathobiology, development of rational tau-based drug therapies calls for a better understanding of the processes leading to dysfunction and neurodegeneration through multidisciplinary approaches across the full spectrum of basic, clinical, and translational research.

• Location: N11-B. F3-07-01
• Tue, Jul 18 (4:15pm - 4:35pm)
• Session chair(s): Jesús Ávila, Khalid Iqbal

Author Block: Jesus Avila, PhD1,2; Marta Bolós, PhD2,3; Mar Perez, PhD4; Juan Perea, MD1,2 and Félix Hernandez, PhD1,2, (1) CIBERNED, Madrid, Spain, (2) Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain, (3) CIBERNED, Madtid, Spain, (4) Universidad Autónoma de Madrid, Madrid, Spain.

Background:

One of the neuropathological hallmarks of AD is an increase in the intracellular amount of tau. In order to revert that increase, one mechanism used by cells could be the secretion of tau to the extracellular space. It has been postulated that under physiological conditions, an increase in the intracellular amount of tau facilitates its secretion to the extracellular space. Extracellular tau can be toxic and can propagate through its interaction with neuronal or glia cells.

In this presentation we will comment on: a) the regions of tau molecule that could be involved in the protein secretion when it is in monomeric form. Those tau regions could be different to those needed for the secretion of truncated or aggregated tau; b) some mechanisms for the interaction of extracellular tau with neuronal and microglia cells.

Methods:

1. COS-7 cell line was used as an in vitro model. Cells were transfected with different tau constructs.
2. Purified tau was added to primary neuron or microglia cultures to study the interaction between tau and these cell types.

Results:

1. N-terminal region of tau molecule could be required for the secretion of soluble intracellular tau.
2. Extracellular monomeric tau could react with specific cell receptors present in neurons or in microglia cells.

Conclusions:

A possible mechanism for monomeric tau secretion and further interactions of tau with neuron or microglia cells is proposed.

• Location: S8. P3-390
• Tue, Jul 18 (9:30am - 4:15pm)
• Session chair(s): Linda Zhang

Subtopic: Optimal neuroimaging measures for early detection.

Keywords: biomarkers, mild cognitive impairment (MCI), normal aging Author Block: Linda Zhang, PhD1; Christopher Long, PhD2;Miguel Medina, PhD3 and Bryan Strange, PhD1,2, (1)Centre for Biomedical Technology, Universidad Politecnica de Madrid, Madrid, Spain, (2)CIEN Foundation, Madrid, Spain, (3)Centre for Networked Biomedical Research on Neurodegenerative Diseases, Madrid, Spain.

Poster