Medicine and Health Sciences Commons^™

Neuroligin-1 Is Altered In The Hippocampus Of Alzheimer's Disease Patients And Mouse Models, And Modulates The Toxicity Of Amyloid-Beta Oligomers, Julien Dufort-Gervais, Chloé Provost, Laurence Charbonneau, Christopher M. Norris, Frédéric Calon, Valérie Mongrain, Jonathan Brouillette

Pharmacology and Nutritional Sciences Faculty Publications

Synapse loss occurs early and correlates with cognitive decline in Alzheimer’s disease (AD). Synaptotoxicity is driven, at least in part, by amyloid-beta oligomers (Aβo), but the exact synaptic components targeted by Aβo remain to be identified. We here tested the hypotheses that the post-synaptic protein Neuroligin-1 (NLGN1) is affected early in the process of neurodegeneration in the hippocampus, and specifically by Aβo, and that it can modulate Aβo toxicity. We found that hippocampal NLGN1 was decreased in patients with AD in comparison to patients with mild cognitive impairment and control subjects. Female 3xTg-AD mice also showed a decreased NLGN1 level …

Ceramide-Enriched Extracellular Vesicles: A Role In Enhancing Amyloid-Beta Neurotoxicity And Mitochondrial Damage In Alzheimer’S Disease, Ahmed Elsherbini

Theses and Dissertations--Physiology

Alzheimer’s disease (AD) is an age-dependent, progressive, neurodegenerative disorder that is characterized clinically by the impairment of cognitive functions concomitant with behavioral and personality changes. AD is associated with distinct pathological hallmarks, namely, intracellular neurofibrillary tangles comprised of hyperphosphorylated tau protein, extracellular amyloid beta (Aβ) plaques, and marked brain atrophy. Besides their main role as the core component of amyloid plaques, oligomeric Aβ have been shown to be neurotoxic. The exact mechanism of Aβ neurotoxicity is yet to be elucidated.

Recently, a pathogenic function of small extracellular vesicles- also known as exosomes- has been proposed, suggesting that exosomes can transfer …