TL;DR
It is illustrated how tauopathy disrupts the preferential maintenance of well-tuned inputs in healthy neural circuitry, resulting in poorly tuned visual responses.
Selective neuronal vulnerability shapes Alzheimer’s disease, but it is commonly inferred from changes in the relative representation of neuronal populations rather than from molecular changes within those populations. We mapped both dimensions across disease progression in amyloid, tau, and combined amyloid-tau mouse m...
Tau aggregation, a defining feature of tauopathies, commonly appears as neuropil threads within neurites including axons. However, the affected neuronal populations and the spatial organization of axonal vulnerability remain poorly defined. Here, following identification of Tau accumulation in parvalbumin (PV) interneu...
Synaptic failure is considered an early driver of Amyotrophic Lateral Sclerosis (ALS), yet identifying the molecular events initiating synaptic decline remains challenging in end-stage human tissue. Here, we exploit the late involvement of the primary visual cortex (Brodmann Area 17 (BA17)) to investigate early disease...
The development of scalable iPSC-neuron models enables tauopathy drug discovery and reconstructs progressive Tau seeding, fibrillization and synaptic dysfunction, and establishes a physiologically relevant, scalable platform for therapeutic screening that connects Tau seed uptake, site-specific phosphorylation, fibril...
The endoplasmic reticulum (ER) extends throughout neurons and regulates many functions, including neurite outgrowth, neurotransmission, and synaptic plasticity. Mutations in ER-shaping proteins cause the neurodegenerative disorder Hereditary Spastic Paraplegia (HSP), yet the ultrastructure and dynamics of neuronal ER r...
Dendritic spine dysfunction may contribute to the etiology and symptom expression of neuropsychiatric disorders. The intimate relationship between spine morphology and function suggests that decoding disease-related abnormalities from spine morphology can aid in developing synapse-targeted interventions. Here, we descr...
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