Research Overview

Alzheimer’s Disease Sequencing Project (ADSP)

Collaboration on Alzheimer’s Disease Research (CADRE): CADRE aims to analyze whole genome sequence data (>60,000) generated by the ADSP incorporating large cohorts of patients and healthy individuals of diverse population groups.  Comprehensive analyses of the combined ADSP data of case-control cohorts and family study designs, the CADRE project aims to enhance understanding of the genetic architecture of Alzheimer’s Disease and to accelerate the search for new therapeutic targets.

 Mitochondria variation with AD, ADRD, and Aging:

Dr. Zhang’s lab is leading this sub-aim by developing methods for calling mitochondria variants, copy numbers from the WGS data, and understanding the role of mitochondria in AD pathology, cognitive decline, and how mitochondrial genetics contribute to AD risk.

ADSP Functional Genomics Consortium (ADSP-FGC)

The Alzheimer’s Disease Sequencing Project (ADSP) Functional Genomics Consortium (FunGen-AD) aims to apply cutting-edge genomics technologies and high-throughput genetic screening to understand the functional impacts underlying the genetic basis of susceptibility and resilience of Alzheimer’s Disease, and to identify genetics-guided targets for the prevention, diagnosis, and treatment of Alzheimer’s disease and related dementias (AD/ADRD). As one of the Core Projects of FunGen-AD, Dr. Zhang’s lab will conduct research about

Circular RNAs and their interactions with RNA-binding proteins to modulate AD-related neuropathology (PIs: Dr. Zhang & Dr. Wolozin)

Goals: This UO1 will leverage large rRNA-depleted RNA-seq data to identify and characterize disease-linked circRNAs and RNA-binding proteins (RBPs), and functional changes in circRNAs or circRNA-RBP interactions that modify AD neuropathology or neurodegeneration.

        ADSP FunGen-xQTL Project

The xQTL project is a collaborative effort across the ADSP-FGC, the AMP-AD, the NIH CARD, and the ADSP. The goal of the xQTL project is to generate a reference map of AD-related quantitative trait loci (QTLs).

A summary of a variety of molecular xQTL studies in human tissues and cells can be found here.

An analysis xQTL pipeline/the ADSP FunGen-xQTL protocol can be found here.

Framingham Heart Study-Brain Aging Program (FHS-BAP) – Project 2

Major goals of the FHS-BAP (U19-AG068753) are to continue surveillance, perform cognitive and MRI exams, and orchestrate the brain donor programs and repository, perform research related to risk, resilience, and inflammatory and vascular basis of AD & Dementia.

In Project 2 (co-led by Drs. Qiu and Zhang), we will evaluate the hypothesis that the link between AD genetic vulnerabilities and chronic peripheral inflammation plays an important role in AD pathogenesis.

Epi-transcriptomic (Methylated RNA) Study in Alzheimer’s Disease 

The role of N6-methyladenosine (m6A) modified RNA in Alzheimer’s disease (PIs: Dr. Wolozin & Dr. Zhang)

This RO1 proposal will investigate a specific type of RNA modification, termed methylation. We will study how RNA methylation changes in Alzheimer’s disease, and whether reducing excessive methylation can delay disease progression and help patients with the disease. Specifically, we will determine how the m6A transcriptome over the disease course in mouse models of AD/ADRD, examining both coding and non-coding RNA (Aim 1), then we will determine how the m6A transcriptome varies by disease severity and type in human pathological cases (Aim 2).  Finally, Aim 3 will determine how m6A contributes to the pathophysiology of tau and neurodegeneration in AD.

DEIA Statements Added to BU Profiles (link)