PLoS ONE (Jan 2012)

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

  • Jerzy Wegiel,
  • Janusz Frackowiak,
  • Bozena Mazur-Kolecka,
  • N Carolyn Schanen,
  • Edwin H Cook,
  • Marian Sigman,
  • W Ted Brown,
  • Izabela Kuchna,
  • Jarek Wegiel,
  • Krzysztof Nowicki,
  • Humi Imaki,
  • Shuang Yong Ma,
  • Abha Chauhan,
  • Ved Chauhan,
  • David L Miller,
  • Pankaj D Mehta,
  • Michael Flory,
  • Ira L Cohen,
  • Eric London,
  • Barry Reisberg,
  • Mony J de Leon,
  • Thomas Wisniewski

DOI
https://doi.org/10.1371/journal.pone.0035414
Journal volume & issue
Vol. 7, no. 5
p. e35414

Abstract

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BackgroundIt 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.Methodology/principal findingsIn 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 (pConclusions/significanceThe higher prevalence of excessive Aβ accumulation in neurons in individuals with early onset of intractable seizures, and with a high risk of sudden unexpected death in epilepsy in autistic subjects with dup(15) compared to subjects with idiopathic ASD, supports the concept of mechanistic and functional links between autism, epilepsy and alterations of APP processing leading to neuronal and astrocytic Aβ accumulation and diffuse plaque formation.