Abnormal intracellular accumulation and extracellular Aβ deposition in idiopathic and Dup15q11.2-q13 autism spectrum disorders.

PloS One
J WeģielThomas Wisniewski

Abstract

It has been shown that amyloid ß (Aβ), a product of proteolytic cleavage of the amyloid β precursor protein (APP), accumulates in neuronal cytoplasm in non-affected individuals in a cell type-specific amount. In the present study, we found that the percentage of amyloid-positive neurons increases in subjects diagnosed with idiopathic autism and subjects diagnosed with duplication 15q11.2-q13 (dup15) and autism spectrum disorder (ASD). In spite of interindividual differences within each examined group, levels of intraneuronal Aβ load were significantly greater in the dup(15) autism group than in either the control or the idiopathic autism group in 11 of 12 examined regions (p<0.0001 for all comparisons; Kruskall-Wallis test). In eight regions, intraneuronal Aβ load differed significantly between idiopathic autism and control groups (p<0.0001). The intraneuronal Aβ was mainly N-terminally truncated. Increased intraneuronal accumulation of Aβ(17-40/42) in children and adults suggests a life-long enhancement of APP processing with α-secretase in autistic subjects. Aβ accumulation in neuronal endosomes, autophagic vacuoles, Lamp1-positive lysosomes and lipofuscin, as revealed by confocal microscopy, indicates that products of enhanc...Continue Reading

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Citations

Feb 13, 2013·Current Opinion in Neurology·Roberto Tuchman
Nov 21, 2015·Epigenomics·Janine M LaSalleStormy J Chamberlain
Sep 4, 2015·Science China. Life Sciences·Rui HuaChen Zhang
Mar 13, 2014·Acta Neuropathologica Communications·Jerzy WegielThomas Wisniewski
Dec 24, 2013·American Journal of Human Genetics·Zongxiao HeSuzanne M Leal
Apr 11, 2017·Biological Psychiatry·Mark D ShenUNKNOWN Infant Brain Imaging Study Network
Oct 26, 2018·Journal of Molecular Neuroscience : MN·Geir BjørklundSalvatore Chirumbolo
Jun 22, 2016·American Journal of Medical Genetics. Part a·Craig A EricksonDebomoy K Lahiri
Dec 14, 2018·Journal of Neurodevelopmental Disorders·Mark D Shen
Sep 28, 2020·Neurochemistry International·Henryk JęśkoAgata Adamczyk
May 31, 2021·Protein & Cell·Hui ZhangGuang-Hui Liu

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Methods Mentioned

BETA
transgenic
confocal microscopy
genotyping

Software Mentioned

EZC1

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