Mutations of the amyloid precursor protein gene are known to be involved in the development of Alzheimer’s disease. Now, new research points to a correlation between this gene and intellectual abilities in children, raising questions about the protein’s role in cognition.

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APP gene variation, which is linked to Alzheimer’s disease, has also been found to correlate to fluid intelligence in children.

According to data provided by the Alzheimer’s Association, approximately 5.5 million people are living with Alzheimer’s disease in the United States. Treatment of the disease is estimated to cost the healthcare system around $259 billion each year. Alzheimer’s accounts for an estimated 70 percent of worldwide dementia cases, suggest the World Health Organization (WHO).

The National Institute on Aging acknowledge several causes for Alzheimer’s disease, including some genetic factors. One feature of Alzheimer’s is a mutation of the gene that encodes amyloid precursor protein (APP), which produces amyloid beta peptides. Amyloid beta forms clusters that build up senile plaques in the brain. Further characteristics and the importance of senile plaques to cognitive functioning are still being researched, however.

A new study – led by Dr. Tetyana Zayats and other researchers from the K.G. Jebsen Centre for Neuropsychiatric Disorders in the Department of Biomedicine at the University of Bergen in Norway – has examined further links between APP and the development of cognitive functions in children.

“Our understanding of biological processes underlying synaptic functioning could be expanded by examining human genetics throughout the lifespan as genetic influences may be the driving force behind the stability of our cognitive functioning,” says Dr. Zayats.

The findings were published in the Journal of Alzheimer’s Disease.

The researchers analyzed data collected from the Avon Longitudinal Study of Parents and Children and the International Genomics of Alzheimer’s Project.

They first looked at the IQ scores and genetic markers of 5,165 children. Following this, the researchers examined the DNA sequence variations of 17,008 adults with Alzheimer’s disease versus 37,154 healthy adults. They also considered the genetic data of 112,151 adults assessed on cognitive functions.

Specifically, Dr. Zayats and her colleagues studied the activity-regulated cytoskeleton-associated protein (ARC), which is associated with neural plasticity – that is, the nervous system’s ability to change and adapt in time.

The researchers found that the ARC gene complex variation was strongly associated with IQ in children. Additionally, it contains the gene that encodes APP, which relates to Alzheimer’s.

Intelligence, Dr. Zayats and her colleagues explain, “captures a broad scope of cognitive abilities” – which are variously defined as combinations of verbal IQ and performance IQ – “often differentiated into crystallized and fluid types.”

Crystallized intelligence refers to accumulated knowledge and skills, and fluid intelligence is linked to problem-solving and the ability to identify patterns.

The researchers found that an APP-encoding gene variation was associated with fluid intelligence in children. The same variation was linked with an Alzheimer’s diagnosis in the adult cohort.

Additionally, analyses of the data collected from adults assessed for cognitive functioning indicated that variations in the APP-encoding gene were linked with reaction time – that is, how long we take to process information.

“This study has potential implications for our understanding of the normal function of these synaptic proteins as well as their involvement in disease,” emphasizes Dr. Zayats.

In some ways, the study confirms associations suggested by previous research. For example, a correlation between intelligence and dementia had already been pointed out, and overproduction of amyloid beta had been noted in the case of people with Alzheimer’s disease and Down syndrome.

The researchers suggest that their study should be followed by additional research, targeting further correlations between gene variations and cognitive functions both in children and in adults.

“Follow-up studies are needed to more precisely determine how variants in APP may exert their effects on cognitive function over a lifespan. Such studies may have valuable implications for our understanding of etiology and, eventually, treatment of disorders associated with cognitive dysfunction, such as [Alzheimer’s disease].”