Tsuneya Ikezu (United States of America)
Mayo Clinic Florida
Department of Neuroscience
Dr. Tsuneya Ikezu is a Professor in the Department of Neuroscience and Director, Molecular NeuroTherapeutics Laboratory at the Mayo Clinic in Florida. Research in the clinic focuses on neuroimmune cell-mediated regulations of neuronal function, neurogenesis, neuroinflammation, and neurodegeneration. Researchers in Dr. Ikezu’s lab are particularly interested in how the innate immune-related cells, extracellular vehicles (EVs), and molecules in the central nervous system (CNS) influence the pathology and progression of select neurodegenerative disorders such as Alzheimer’s disease (AD) and frontotemporal dementia. He has authored more than 109 journal articles, edited the textbook Neuroimmune Pharmacology (Springer Nature) and served on several editorial boards. Over his career, Dr. Ikezu has received Vada Kinman Oldfield Alzheimer’s Research Award (2000), Inge Grundke Iqbal Award from Alzheimer’s Association (2016) and recently Jack Spivack Excellence in Neuroscience Award (2018). Dr. Ikezu received his M.D. and Ph.D. from University of Tokyo School of Medicine, completed post-doctoral trainings at Massachusetts General Hospital and Cleveland Clinic Foundation, and was Professor of Pharmacology and Experimental Neuroscience at University of Nebraska Medical Center prior to joining Boston University (2010-2020) and Mayo Clinic (2021-).

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 Conference Calendar

WOLFRAMIN-1–EXPRESSING NEURONS IN THE ENTORHINAL CORTEX PROPAGATE TAU TO CA1 NEURONS, INDUCE NEUROINFLAMMATION AND IMPAIR HIPPOCAMPAL MEMORY, MIMICKING EARLY BRAAK STAGES OF ALZHEIMER’S DISEASE

Session Name
1530 - TAU PROPAGATION AND CELLULAR INTERACTIONS 2 (ID 72)
Session Type
SYMPOSIUM
Date
Sat, 19.03.2022
Session Time
09:10 AM - 11:10 AM
Room
ONSITE: 114
Lecture Time
09:40 AM - 09:55 AM
Presenter

Abstract

Aims

We have recently reported that wolframin-1-expressing (Wfs1+) pyramidal neurons in the layer II entorhinal cortex (ECII) that project to the CA1 propagate phosphorylated tau (pTau) via the temporoammonic pathway in a mouse model (ECII-CA1 tau mouse), mimicking early stages of tau pathology in early-stage Alzheimer’s disease (AD). We examined if this phenomenon is recapitulated in human brains. Using the mouse model, we characterized tau transfer between ECII axons and CA1 dendrites and determined the pathological phenotype via multi-modal approaches.

Methods

Human brain tissues from 12 postmortem early-stage AD cases were examined for Wfs1 and pTau expression. ECII-CA1 tau mice were developed using Wfs1-Cre mice injected with Cre-inducible AAV expressing human P301L mutant tau in the ECII. At 4 weeks post-injection, the mice underwent behavioral tests and their brains were subject to immunohistochemistry, electrophysiology, electron microscopy, and RNA-sequencing analysis.

Results

High numbers of pTau+ Wfs1+ neurons were detected in EC of human brains at early-stage AD stages. The ECII-CA1 tau mice displayed tau pathology specifically propagating in CA1, avoiding the dentate gyrus. Reduced measures of excitability in the CA1, determined by field recording and multielectrode array, were accompanied by deficits in trace and contextual memory and enhanced expression of neuroinflammatory genes.

Conclusions

Wfs1+ pyramidal neurons are conserved in the human EC and contain pTau in early AD stages. The ECII-CA1 tau mice mimic early Braak stages of AD in tau propagation to the CA1 via monosynaptic transmission, accompanied by neuroinflammation and cognitive deficits.

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