Effect of amyloid beta in choline metabolism
November 2017
University of Western Ontario, London, Canada
The impaired function of cholinergic neurons is a main factor in Alzheimer's disease-related cognitive decline. Deficits in the normal homeostasis of high-affinity choline transporter lead to impaired cholinergic neurotransmission due to disturbed choline homeostasis. Amyloid beta, an important driver of Alzheimer's pathology, has been shown to impair normal synaptic transmission. Here, the role of amyloid-beta peptides on choline metabolism is studied using a human neuroblastoma cell line. The researchers show that amyloid-beta decreases choline uptake and reduces the amount of high-affinity choline transporter on the cell membrane through disruption of its normal recycling. Lysosomal inhibition could counteract this effect but did not avoid amyloid-beta effects on the transporter's activity. Finally, the researchers could ameliorate the pathological phenotype with the use of antibodies directed to the mid-region of amyloid-beta peptide, indicating a specific epitope or conformation responsible for this behaviour. Overall, this study reveals valuable mechanistic insights into amyloid beta's disruption of choline homeostasis in a human model that can be potentially used in further studies to better direct the therapeutic strategies towards more effective targets.
Amino-terminal β-amyloid antibody blocks β-amyloid-mediated inhibition of the high-affinity choline transporter CHT
R Jane Rylett
Added on: 08-17-2021
[1] https://www.frontiersin.org/articles/10.3389/fnmol.2017.00361/full[2] https://data.jrc.ec.europa.eu/dataset/a8fd26ef-b113-47ab-92ba-fd2be449c7eb
