Register below for our weekly Letter from the Editor to receive the latest Clinical Lab news and insights.
Email

Neuropathologists' genetic discovery fills in Alzheimer's gaps

By LabPulse.com staff writers

November 26, 2019 -- A new study sheds light on the significance of the Mucin 6 (MUC6) gene in late-onset Alzheimer's disease (LOAD), helping to fill gaps left by prior genetic studies, researchers recently reported in the Journal of Neuropathology & Experimental Neurology.

The discovery came through the analysis of data from more than 10,000 people involved in the Alzheimer's Disease Sequencing Project and included a separate cohort of autopsied subjects with digital pathology data.

Dr. Peter Nelson, PhD, director of neuropathology at the University of Kentucky, and colleagues discovered a genetic variation within a segment of the MUC6 gene and located immediately downstream from another gene called Adaptor Related Protein Complex 2 Subunit Alpha 2 (AP2A2) (J Neuropathol Exp Neurol, November 4, 2019).

Using polymerase chain reaction (PCR) analyses of DNA samples, they correlated genetic features with the severity of Alzheimer's-type brain pathology. In addition, subjects with longer MUC6 variable number tandem repeat (VNTR) regions had lower AP2A2 expression.

Genome-wide association studies have not told the whole story about heritable factors in Alzheimer's disease; for example, some left out rare gene variants, the authors noted. In fact, past studies have suggested that many genetic risk factors associated with late-onset Alzheimer's disease -- perhaps one-half -- remain unidentified, according to Nelson.

"Correspondingly, a lot of the genome has not been analyzed due to the complexity of the human genome and shortcomings in sequencing technology," he commented by email.

The study suggests a strong association between the variant and the disease, but the sample size was small and results need to be replicated in other groups, according to Nelson.

AAIC update: Where blood-based dementia tests stand in 2019
Against the shadowy backdrop of multiple failed trials in Alzheimer's disease, hope springs eternal for a reliable, noninvasive blood test for dementia,...
Evidence builds for Alzheimer's beta-amyloid blood test
Blood-based biomarker testing for Alzheimer's disease performed well in two prospective studies for assessing beta-amyloid plaque buildup in the brain....
NIH study outlines pathology of newly defined dementia disorder
Researchers with the U.S. National Institutes of Health (NIH) have defined the pathology of a common dementia disorder that mimics Alzheimer's disease...

Copyright © 2019 LabPulse.com