2 AD markers correlate with aggression in ASD

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Two Alzheimer Markers: Amyloid Precursor Protein and Acetylcholinesterase

Correlate with Aggression in Autism

Deborah K. Sokol, Debomoy K. Lahiri, Darlene Kardatzke, Maloney, DeMao

Chen. Neurology; Psychiatry; Pediatrics, Indiana University School of Medicine,

Indianapolis, IN.

BACKGROUND: Phenotype similarities between Alzheimer disease (AD) and autism

such as language and behavioral disturbance have led to the study of AD

biochemical markers in autism. AD is associated with low levels of amyloid

precursor protein (APP) and acetylcholine (measured indirectly by serum

acetylcholinesterase-AChE). We hypothesized that APP and AChE would correlate

with abnormal autistic behavior.

OBJECTIVE: To measure APP and AChE levels and correlate these with clinical and

cognitive function in children with autism.

DESIGN/METHODS: Eleven children with autism (8 male) meeting DSM-IV criteria,

ages 43-63 months and seven typical developing controls (five male), ages 37-71

months. All plasma samples were run on 10% SDS-Page, transferred to

nitrocellulose membrane and probed with 22C11 antibody to total soluble APP.

Clinical features were measured by the Childhood Autism Rating Scale and

Autistic Diagnostic Interview-Revised (ADI-R). Cognitive function and

socioeconomic status (SES) were assessed by the Mullen Scales of Early Learning

(MSEL) and the Hollingshead Index, respectively.

RESULTS: Groups did not differ in age, race, sex, medication use, or SES. There

were no significant differences for APP or AChE levels between the groups. For

all autistic children, APP correlated with ADI-R measurement of aggression,

regression and self inflicted injury (r=0.83, p<0.05), especially for severely

autistic children (r=0.90; p<0.05). A negative correlation was found for APP and

more introverted, restricted behavior (ADI-R-C total) for all autistic children.

APP was negatively correlated with SES (r=-0.84,p<0.05) for severely autistic

children. Among non-autistic children, a negative correlation (r=-0.76,p<0.05)

was found between APP levels and cognitive function (MSEL composite score). AChE

correlated with ADI-R aggression (r=0.61, p<0.05), for all autistic children.

CONCLUSIONS: High levels of APP and AChE may distinguish an autism with

aggression subtype. As APP is neurotrophic, this supports the brain overgrowth

hypothesis in autism as suggested by neuroimaging, neuropathology, and serology

studies. Severely autistic children with higher APP were of lower SES. APP may

effect learning as evidenced by the association of low APP to higher cognitive

function in non-autistic subjects.