Investigators Identify Gene Linking Cataracts and Alzheimer’s Disease.

In a recent study, investigators at the BU Schools of Medicine and Public Health have identified a gene linking age-related cataracts and Alzheimer’s disease. The findings, published online in PLoS ONE, contribute to a growing body of evidence showing that these two diseases, both associated with increasing age, may share common etiologic factors.

Gyungah Jun, PhD, from the departments of medicine, ophthalmology and biostatistics at BUSM and BUSPH, served as the study’s lead author. The senior author was Lindsay A. Farrer, PhD, professor of medicine, neurology, ophthalmology, genetics & genomics, epidemiology and biostatistics and chief of the Biomedical Genetics Section at BUSM.

Using the Framingham Offspring Eye Study cohort, investigators looked at brain MRI findings on or after 10 years from an original eye exam and concluded that there was a significant correlation between a quantitative measure of cortical cataract and several Alzheimer’s disease-related measures of brain degeneration. Particularly affected was the volume of the temporal horn, which is a brain structure that is progressively enlarged in patients with Alzheimer’s disease. Researchers also found a strong correlation between cortical cataract formation and poorer performance on several cognitive tests administered at the time of the MRI scan.

With such a link not confounded by age or sex, the investigators then performed a genome-wide association study looking at nearly 190,000 single-nucleotide polymorphisms (SNPs), or DNA sequence variations. Three intronic (non-coding) SNPs in the gene encoding δ-catenin came to the fore. This protein is a key component in cell adherence and formation of cell junctional structures.

“Though much work remains to be done, a link between cataracts and Alzheimer’s disease supports the idea of a systemic, rather than brain-limited, focus for processes leading to Alzheimer’s disease,” said Farrer. “This study gives hope that we are moving toward earlier diagnosis and new treatment targets for this debilitating disease.”

Other researchers on the study include: Juliet Moncaster, PhD, from the department of psychiatry; Sudha Seshadri, MD, from the department of neurology and associate professor of the Framingham Heart Study; Jacqueline Buros, from the department of medicine; Ann C. McKee, MD, from the departments of neurology, pathology and laboratory medicine, the BU Alzheimer’s Disease Center, and the Bedford Veterans Administration Hospital; and Phillip A. Wolf, MD, of the departments of neurology and epidemiology and professor of the Framingham Heart Study of BUSM and BUSPH. Researchers from the University of Toronto, the Bedford Veterans Administration Hospital, the Universití Laval and the University of Cambridge also contributed.

Submitted by: Lisa Chedekel

chedekel@bu.edu