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academies

March 14-16, 2019 | London, UK

International Conference on

Vascular Dementia and Dementia

Neurological Disorders and Stroke

Joint Event

Journal of Brain and Neurology | Volume 3

Analysis of Tau in neuron-derived extracellular vesicles

Francesc X Guix1, Grant T Corbett1, Diana J Cha1, Maja Mustapic2, Wen Liu1, David Mengel1, Zhicheng Chen1, Dimitrios Kapogiannis2, Elena

Aikawa3, Tracy Young-Pearse1, Dennis J Selkoe1, and Dominic MWalsh1

1Laboratory for Neurodegenerative Disease Research, Ann Romney Center for Neurologic Diseases, Brigham & Women’s Hospital and Harvard Medical

School, Boston, USA

2Laboratory of Neurosciences, National Institute on Aging, NIH, Baltimore, USA

3Center for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Brigham & Women’s Hospital and Harvard Medical School,

Boston, USA

Introduction: Recent Alzheimer’s disease (AD) drug trials have

highlighted a need for better diagnosis of study participants,

and the development of biomarkers that canbe used tomonitor

response to therapy.Measurement of tau and the amyloid beta-

protein in cerebrospinal fluid (CSF) is unpopular with patients,

and quantitation of amyloid by PET imaging is expensive. Thus,

there is an urgent need for less costly and intrusive, and more

widely available, blood-based biomarkers. Measurement of the

tau and A in brain-derived blood-borne extracellular vesicles

(EVs) should reflect changes occurring in the brain. In addition,

EVs have been proposed to drive the spread of neurofibrillary

tangles (NFTs) pathology in AD brains. Thus, measurement

of tau in EVs may both facilitate biomarker development and

provide insight on the molecular pathology of AD. Methods:

We used differential centrifugation to isolate and characterize

exosomes from cultured primary and iPSC-derived neurons

(iNs), as well as from human CSF and plasma. Since the MTBR

domain of tau is known to drive aggregation, we set out to

determine whether MTBR-containing forms of tau are present

in neural EVs. Results: In medium from 2 different iN lines, we

detected MTBR-containing tau in exosomes at very low levels.

Analysis of the exosomes pellet from CSF revealed low levels

of tau, equivalent to ~0.1 pg per ml of CSF. As was evident with

EVs from cultured neurons and CSF, neurally-derived exosomes

from human plasma also contained aggregation-competent

tau. Conclusions: Exosomes contain aggregated-competent tau,

but further studies will be required to examine the potential for

tau-containing exosomes to seed aggregation in the recipient

cells.