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Pizza and soft drinks will be providedÌýafter the seminar, courtesy of the BIC director (strictly for attendees of the seminar).

Jonathan Gallego Rudolf

A collaboration between the Baillet Lab and the Villeneuve Lab

Synergistic association of Aβ and tau pathology with cortical neurophysiology and cognitive decline in asymptomatic older adults

Animal and computational models of Alzheimer’s disease (AD) indicate that early amyloid-β (Aβ) deposits drive neurons into a hyperactive regime, and that subsequent tau depositions manifest an opposite, suppressive effect as behavioral deficits emerge. Here we report analogous changes in macroscopic oscillatory neurophysiology in the human brain. We used positron emission tomography and task-free magnetoencephalography to test the effects of Aβ and tau deposition on cortical neurophysiology in 104 cognitively unimpaired older adults with a family history of sporadic AD. In these asymptomatic individuals, we found that Aβ depositions colocalize with accelerated neurophysiological activity. In those also presenting medial–temporal tau pathology, linear mixed effects of Aβ and tau depositions indicate a shift toward slower neurophysiological activity, which was also linked to cognitive decline. We conclude that early Aβ and tau depositions relate synergistically to human cortical neurophysiology and subsequent cognitive decline. Our findings provide insight into the multifaceted neurophysiological mechanisms engaged in the preclinical phase of AD.

Jonah Kember

Chai Lab

Developmental changes in diffusion markers of neurite across the hippocampus

The hippocampus is a critical structure supporting the encoding and retrieval of episodic memories, yet the intricate development of its microstructure in humans remains unknown. Understanding this microstructural maturation may provide critical insight into the basic mechanisms underlying memory and their disruption in disease. To address this gap, we non-invasively estimated the density and branching complexity of neurites (dendrites, axons, glial processes) using diffusion-weighted MRI in 364 participants aged 8–21. With development, we observed large increases in neurite density and branching complexity that persisted until late adolescence. Increases in neurite density were relatively homogenous across hippocampal subfields and the longitudinal axis. Increases in branching complexity were heterogeneous, increasing primarily in CA1, SRLM, Subiculum, and increasing along a gradient from posterior to anterior hippocampus. To contextualize these findings, we sought to understand the cellular composition of hippocampal tissue which exhibited these developmental changes in neurite. To do so, we constructed an atlas of 34 hippocampal cell-types by integrating previously processed data from single-nuclei RNA sequencing of the human hippocampus with the Allen Human Brain atlas. Then, we identified 6 spatial components (mixtures of cell-types which vary across the hippocampus) in this atlas, and spatially correlated these components with age-related changes in neurite. We found that age-related changes in neurite density spatially overlapped with a granule cell component, whereas age-related changes in neurite branching complexity overlapped with a pyramidal neuron component. These results provide the first glimpse at the nonlinear maturation of hippocampal microstructure in humans and describe the cell-type composition of hippocampal tissue which exhibits these changes.