alzheimer’s/dementia

E2 Gene May Offer Some Protection Against Cognitive Decline

New genetic analyses reveal that this gene is associated with a slower rate of cognitive decline with age.

The APOE gene—coding for a protein involved in lipid transport and linked to the clearance of amyloid-beta, a protein that builds up in the brain in Alzheimer’s disease—exists in three forms: E4, E3, and E2.

A new study led by a School of Public Health researcher and published in the Journal of Alzheimer’s Disease shows evidence that the E2 gene is associated with a slower rate of cognitive decline with age.

“A lot of attention is paid to genetic traits that put people at higher risk for diseases like Alzheimer’s, but understanding genetic traits that seem protective against cognitive decline is also valuable,” says study lead author Benjamin Sweigart, a doctoral student in the Department of Biostatistics.  “Our results suggest that the E2 allele may play a particularly important biochemical role in slowing cognitive decline. Understanding exactly what it does could help advance the development of therapeutics that slow cognitive decline as we age.” 

To better understand the role of E2 in mediating cognitive decline, Sweigart and colleagues analyzed genotype data from two large longitudinal cohort studies: the New England Centenarian Study and the Long Life Family Study. The New England Centenarian Study includes over 4,000 participants comprised of centenarians and their family members. The Long Life Family Study has enrolled about 4,900 participants belonging to long-lived families. These two samples provided the researchers with a sizeable group of individuals carrying the E2 allele.

To determine the effect of E2 allele status on cognitive decline, the researchers used a tool called the Telephone Interview for Cognitive Status (TICS). Every three years in the Long Life Family Study (or, for participants over age 70, every year) and every other year for participants in the New England Centenarian Study, the researchers administered this series of questions designed to screen for cognitive impairment.

After analyzing the genotypes of the participants and comparing their scores on TICS, the researchers found that individuals homozygous for the genotype (E2/E2 individuals) experienced a significantly slower rate of cognitive decline as they got older. None of the other genotypes, however, were significantly different than the E3/E3 genotype. individuals with only one E2 allele (heterozygous individuals) did not have the same protective effect as individuals with two E2 alleles (homozygous individuals).

“These findings are consistent with a protective effect of the E2/E2 genotype on episodic memory, working memory, and executive function domains of cognitive function,” Sweigart says.

The study was co-authored by Stacy L. Andersen and Thomas T. Perls of the Section of Geriatrics of the Boston University School of Medicine, Anastasia Gurinovich and Paola Sebastiani of the Institute for Clinical Research and Health Policy Studies of Tufts Medical Center, and Stephanie Cosentino and Nicole Schupf of the Cognitive Neuroscience Division of the Department of Neurology and Taub Institute for Research on Alzheimer’s Disease and the Aging Brain and the Gertrude H. Sergievsky Center at Columbia University.