Format

Send to

Choose Destination
J Alzheimers Dis. 2017;59(2):723-735. doi: 10.3233/JAD-170049.

Implication of the APP Gene in Intellectual Abilities.

Author information

1
K.G. Jebsen Centre for Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway.
2
Department of Psychiatry, Haukeland University Hospital, Bergen, Norway.

Abstract

BACKGROUND:

Cognitive functions are highly heritable and polygenic, though the source of this genetic influence is unclear. On the neurobiological level, these functions rely on effective neuroplasticity, in which the activity-regulated cytoskeleton associated protein (ARC) plays an essential role.

OBJECTIVES:

To examine whether the ARC gene complex may contribute to the genetic components of intellectual function given the crucial role of ARC in brain plasticity and memory formation.

METHODS:

The ARC complex was tested for association with intelligence (IQ) in children from the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 5,165). As Alzheimer's disease (AD) shares genetics with cognitive functioning, the association was followed up in an AD sample (17,008 cases, 37,154 controls).

RESULTS:

The ARC complex revealed association with verbal and total IQ (empirical p = 0.027 and 0.041, respectively) in the ALSPAC. The strongest single variant signal (rs2830077; empirical p = 0.018), within the APP gene, was confirmed in the AD sample (p = 2.76E-03). Functional analyses of this variant showed its preferential binding to the transcription factor CP2.

DISCUSSION:

This study implicates APP in childhood IQ. While follow-up studies are needed, this observation could help elucidate the etiology of disorders associated with cognitive dysfunction, such as AD.

KEYWORDS:

APP; ARC; Alzheimer’s disease; Avon Longitudinal Study of Parents and Children; dementia; intelligence; synaptic plasticity

PMID:
28671113
PMCID:
PMC5523840
DOI:
10.3233/JAD-170049
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for IOS Press Icon for PubMed Central
Loading ...
Support Center