News and Updates
June 1, 2023 - Study author Dr. Lindsay Farrer, and other researchers including Dr. Donghe Li and Dr. John Farrell, had their article, Novel loci for Alzheimer's disease identified by a genome-wide association study in Ashkenazi Jews, published in the journal Alzheimer's & Dementia.
Farrer and his colleagues conducted a genome-wide association study for AD in a sample of 3,500 people whose ancestry was almost exclusively Ashkenazi Jewish, including roughly equal numbers of persons with AD and cognitively normal individuals who were identified in a much larger group of EA (European ancestry) participants in large national AD genetics studies using an approach that compared genetic signatures with members of an Ashkenazi Jewish reference sample.
“Our study illustrates the greatly increased power for detection of genetic associations in communities like Ashkenazi Jews who trace their lineage to a relatively small group of ancestors," said Farrer. "In such communities, disease-associated variants may be much more frequent compared to samples ascertained from large, mixed populations".
Trans-ethnic studies have shown that population differences in genetic background can be leveraged to make novel discoveries that might require a sample size several orders of magnitude larger to achieve similar success studying a single population, according to the study.
“Similarly, studies of small samples from founder populations (ethnic or religious groups whose origins can be traced to a limited number of ancestors and thus have a more homogeneous genetic background) have successfully detected robust and subsequently validated associations of AD with several genes,” the researchers wrote.
The researchers identified several genetic risk factors for AD, including some previously known (APOE, TREM2) and several novel ones that are strong biological candidates (RAB3, SMAP2, ZNF890P, SPOCK3, GIPR). Study author Dr. Lindsay Farrer said there are lessons to be learned here about genetic diseases in communities with a smaller gene pool. He said the genes highlighted by the study could be relevant to diagnosing and treating Alzheimer's in other populations.
Dr. Farrer’s Radio Interview SiriusXM-Doctor Radio’s Internal Medicine show hosted by Dr. Ira Breite (NYU Langone Health)
January 9, 2023, Dr. Farrer and Dr. Subramanian were featured guests on SiriusXM-Doctor Radio’s Internal Medicine show hosted by Dr. Ira Breite (NYU Langone Health, gastroenterologist & Clinical Associate Professor of Medicine).
The talk discussed the recent study on the relationship between age-related macular degeneration as a risk factor for COVID-19 infection and severe disease.
Age-Related Macular Degeneration a Risk factor for Covid-10 Infection
Recent evidence has emerged to suggest that age-related macular degeneration (AMD) is a clinical risk factor for increased risk for infection and mortality. AMD has been reported to confer higher risk of severe complications of SARS-CoV-2 infection, including respiratory failure and death (25 percent), a risk which is higher than Type 2 diabetes (21 percent) and obesity (13 percent).
Considering these observations, researchers from Boston University Chobanian & Avedisian School of Medicine hypothesized that AMD and COVID-19 share common genetic risk factors and designed and executed a study that identified a novel association of the two diseases with variants in the PDGFB gene. This gene encodes a platelet derived growth factor (PDGF) which has a role in the formation of new blood vessels and is involved in the abnormal blood vessel changes that occur in AMD. They also found that more severe COVID-19 outcomes were associated with AMD likely arising from genetic predisposition to dysfunction involving complement proteins, as well as with a higher level of PDGF in blood serum.
“Our findings add to the body of evidence for the increased risk of infection and mortality from COVID-19 among AMD patients. Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” explained co-corresponding author Lindsay A. Farrer, PhD, chief of biomedical genetics. Read more here
Dr. Xiaoling Zhang interview with Medical News Today: Risk of Alzheimer’s linked to cholesterol, blood sugar levels at age 35
March 29, 2022, Dr. Xiaoling Zhang interviewed with Annie Lennon from Medical News Today, and discussed about the recent study published in Alzheimer's and Dementia: The Journal of the Alzheimer's Association, Farmingham Heart Study.
Dr. Xiaoling Zhang told MNT that improved blood flow in the brain might also explain some of their findings.
She explained that HDL could increase transportation and thus reduce the accumulation of amyloid-beta plaques, which are protein build-ups characteristic of AD.
When asked about the link between AD and glucose levels, Dr. Zhang said that higher glucose levels in the blood are linked to higher brain glucose concentrations and more severe plaques in AD brains.
Find more information of the interview here.
On Wednesday, March 23, 2022, Dr. Lindsay Farrer interviewed with Sandee LaMotte from CNN, and discussed about the recent study published in Alzheimer's and Dementia: The Journal of the Alzheimer's Association, Farmingham Heart Study.
"What's unique about the study is the large sample of individuals that are examined every four years or so, starting at age 35, and followed into the age when an Alzheimer's diagnosis may occur," Farrer said.
According to the Study, People 35 to 50 could lower their Alzheimer's risk by 15.4% if they raised their high-density lipoprotein, or HDL, by 15 milligrams per deciliter. People between the ages of 51 and 60 who raised their HDL reduced their risk by 17.9%.
Identifying Brain Epitranscriptomic Changes Associated with Alcohol Use Disorder
Huiping Zhang, PhD
Award Number: 1R01AA029758-01
Chronic alcohol consumption may result in methyl-adenosine modification of brain RNAs, thus altering the stability and expression of brain RNAs involved in reward or addiction-related pathways. This R01 project will (1) identify differentially methylated and expressed messenger RNAs (mRNAs) in multiple regions of postmortem brains of subjects with alcohol use disorder (AUD), (2) validate AUD-associated brain mRNA methylation and expression changes by mouse modeling, and (3) confirm the effect of AUD-associated brain mRNA methylation changes on mRNA expression and neuronal activity by an innovative epitranscriptome editing approach. The findings will provide insight into a novel epitranscriptomic mechanism of AUD and facilitate the design of a novel AUD therapeutic strategy through altering the methylation status of specific mRNAs.
Here for more information about the research
Congratulation to Dr. Huiping Zhang who has recieved the 2022 Wing Tat Lee Award
Dr. Zhang will collaborate with Ying Liu, PhD, associate professor of genetics at Soochow University, to study the genetic mechanism of 22q11.2 deletion syndrome (22q11.DS), which is a disorder characterized by heart abnormalities, recurrent infections and distinctive facial features. They will use genome editing techniques to study the function of genes and genetic variants within the 22q11.2 deletion region. Functional genetic variants identified in this deletion region could be useful diagnostic biomarkers for 22q11.DS
Circular RNAs and their interactions with RNA-binding proteins to modulate AD-related neuropathology
Dr. Xiaoling Zhang awarded NIH 1U01 Research Project grant
New variants, especially in non-coding regions, are expected to be discovered through the ongoing Alzheimer’s Disease Sequencing Project (ADSP). In 2020, NIA launched the ADSP Functional Genomics Initiative (RFA-AG-21-006) to strengthen the translational pathways leading from genetic variations to potential targets. In collaboration with Dr. Benjamin Wolozin in the Department of Pharmacology, we recently received a NIA U01 award ($3.6M) to identify circular-RNAs and their interactions with RNA-binding proteins to modulate AD-related neuropathology. This is one of the six awarded core projects of the new ADSP Functional Genomics Consortium (ADSP-FGC) which was established in August 2021.
This proposal will investigate circular RNAs (circRNAs) and RNA binding proteins (RBPs) that regulate or are regulated by these circRNAs. Recent genomic studies have discovered thousands of circRNAs produced from both protein-coding genes and non-coding regions of the genome via a process known as back-splicing. The discovery of circRNAs opens an entirely new window into mechanisms of neurodegeneration in AD and related dementias (AD/ADRD). This proposal seeks to identify and characterize disease-linked circRNAs and RBPs, and functional changes in circRNAs or circRNA-RBP interactions that modify ADRD neuropathology or neurodegeneration. Successful discovery of key circRNAs or circRNA-RBP interactions in aging human brains could uncover novel biomarkers, disease mechanisms, or therapeutic targets to diagnose, mediate, or prevent the progression of AD/ADRD. Read More Here
Exploring mechanisms driving microbe-induced AD risk using next generations sequence data
Dr. Richard Sherva awarded NIH R01 grant
Multiple lines of evidence suggest microbial infections are risk factors for Alzheimer’s disease (AD). Amyloid-β (Aβ) peptides possess antimicrobial activity and may protect against human herpes viruses (HHV). Viral DNA is also detectable in Aβ plaques, and HHV DNA detected in next generation sequencing (NGS) experiments is associated with AD risk. Read More Here