4,068 posters, 219 videos, 101 topics, 69 sessions, 14,365 authors, 6,128 institutions

Alzheimer's Association International Conference 2026

July 12-15, 2026 | London, United Kingdom, and Online

9463

Long Distance Neurodegenerative Signaling Mediated By Neurotrophin Receptor P75NTR

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Poster Presenter

Amrita Pathak

Authors

Amrita Pathak, Hrishita Das, Pooja Shukla, Anthony Spano, Austin Keeler, Christopher Deppmann, Bruce Carter

Affiliations

1Vanderbilt Brain Institute, Vanderbilt Univ. SOM Basic Sciences, Nashville 2Current address: Inst. of Neuropsychology & Neurosciences, Amity Univ. Noida, India, 1Vanderbilt Brain Institute, Vanderbilt Univ. SOM Basic Sciences, Nashville, TN, USA, Inst. of Neuropsychology & Neurosciences, Amity Univ. Noida, India, Dept. of Biology, Univ. of Virginia, Charlottesville, VA, USA, Dept. of Biology, Univ. of Virginia, Charlottesville, VA, USA; Current address: Dept. of Biological Sciences, Univ. of Delaware, Newark, Vanderbilt Brain Institute, Vanderbilt Univ. SOM Basic Sciences, Nashville, TN, USA

Part of Topic

Introduction:

§Neurotrophin signaling governs the balance between neuron survival & death.

§Increased expression of pan neurotrophin receptor p75NTR and proneurotrophin, proNGF has been reported in post mortem brain of Alzheimer’s disease (AD) patients and mice models.

§Mature neurotrophins bind to their cognate receptor tyrosine kinases to promote long range retrograde survival signaling from distal axons (DA) to the cell body (CB) by forming “signaling endosomes”.

§On the contrary, p75NTR activation in distal axons results in retrograde apoptotic signaling in neurons which has been recently realized.

§Despite extensive research on retrograde survival signaling by neurotrophins, the mechanisms for retrograde death signaling mediated by p75NTR remains unclear.

§Here we investigated degenerative signaling endosome biogenesis and their long-distance transport resulting in neuron death. Understanding this mechanism may provide insights into neuron death in Alzheimer’s disease.

Summary and Conclusion:

§Localized cleavage of p75NTR within axons generated p75ICD as a retrograde death signal.

§P75NTR palmitoylation represents a mechanism for attaching p75ICD to the retrograde transport vesicles resulting in biogenesis of degenerating signaling endosomes and long distance death signaling in neurons.

§Current efforts are focused on determining the role of p75NTR palmitoylation in cholinergic neuron death to understand the mechanism of Alzheimer’s disease onset and progression.

§In light of evidence for disrupted neurotrophin signaling in AD and our demonstration of p75ICD as a degenerative signal, axonal transport of both pro-survival and pro-apoptotic signals must be considered in designing therapeutic strategies.

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