High levels of Alzheimer beta-amyloid precursor protein (APP) in children with severely autistic behavior and aggression.
Autism is characterized by restricted, repetitive behaviors and impairment in socialization and communication. Although no neuropathologic substrate underlying autism has been found, the findings of brain overgrowth via neuroimaging studies and increased levels of brain-derived neurotrophic factor (BDNF) in neuropathologic and blood studies favor an anabolic state. We examined acetylcholinesterase, plasma neuronal proteins, secreted beta-amyloid precursor protein (APP), and amyloid-beta 40 and amyloid-beta 42 peptides in children with and without autism. Children with severe autism and aggression expressed secreted beta-amyloid precursor protein at two or more times the levels of children without autism and up to four times more than children with mild autism. There was a trend for children with autism to show higher levels of secreted beta-amyloid precursor protein and nonamyloidogenic secreted beta-amyloid precursor protein and lower levels of amyloid-beta 40 compared with controls. This favors an increased alpha-secretase pathway in autism (anabolic), opposite to what is seen in Alzheimer disease. Additionally, a complex relationship between age, acetylcholinesterase, and plasma neuronal markers was found.
Sokol
Deborah K
DK
Department of Neurology, Indiana University School of Medicine, 702 Barnhill Drive, Indianapolis, IN 46202, USA. dksokol@iupui.edu
Chen
Demao
D
Farlow
Martin R
MR
Dunn
David W
DW
Maloney
Bryan
B
Zimmer
Jennifer A
JA
Lahiri
Debomoy K
DK
D000110:Acetylcholinesterase / Q000097:blood*; D000293:Adolescent; D000374:Aggression; D016229:Amyloid beta-Peptides / Q000097:blood*; D016564:Amyloid beta-Protein Precursor / Q000097:blood*; D001321:Autistic Disorder / Q000097:blood* / Q000523:psychology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D012720:Severity of Illness Index
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D000110:Acetylcholinesterase