The fusiform gyrus exhibits an epigenetic signature for Alzheimer’s disease

Abstract

Background: Alzheimer's disease (AD) is the most common type of dementia, and patients with advanced AD frequently lose the ability to identify family members. The fusiform gyrus (FUS) of the brain is critical in facial recognition. However, AD etiology in the FUS of AD patients is poorly understood. New analytical strategies are needed to reveal the genetic and epigenetic basis of AD in FUS. Results: A complex of new analytical paradigms that integrates an array of transcriptomes and methylomes of normal controls, AD patients, and "AD-in-dish" models were used to identify genetic and epigenetic signatures of AD in FUS. Here we identified changes in gene expression that are specific to the FUS in brains of AD patients. These changes are closely linked to key genes in the AD network. Profiling of the methylome (5mC/5hmC/5fC/ 5caC) at base resolution identified 5 signature genes (COL2A1, CAPN3, COL14A1, STAT5A, SPOCK3) that exhibit perturbed expression, specifically in the FUS and display altered DNA methylome profiles that are common across AD-associated brain regions. Moreover, we demonstrate proof-of-principle that AD-associated methylome changes in these genes effectively predict the disease prognosis with enhanced sensitivity compared to presently used clinical criteria. Conclusions: This study identified a set of previously unexplored FUS-specific AD genes and their epigenetic characteristics, which may provide new insights into the molecular pathology of AD, attributing the genetic and epigenetic basis of FUS to AD development.

Multimodal data integration via mediation analysis with high‐dimensional exposures and mediators

“…The fusiform gyrus is critical in facial recognition. Alterations of gene expression specific to the fusiform gyrus were discovered in AD patients (Ma et al, 2020). The left middle temporal gyrus is related to the recognition of known faces and accessing word meaning while reading (Acheson & Hagoort, 2013).…”

Research on Frequent Itemset Mining of Imaging Genetics GWAS in Alzheimer’s Disease

“…In addition, this was considered to affect the progression and diagnosis of many degenerative diseases, such as AD, chronic traumatic encephalopathy, and Lewy body diseases [ 50 , 51 ]. In the research of Dingailu et al [ 52 ], the fusiform gyrus showed the epigenetic characteristics of AD. Mario et al [ 53 ] reviewed the experimental and humans studies, and summarized the evidence linking temporal epileptiform activity, network hyperexcitability, and AD.…”

CAPN3: A muscle‑specific calpain with an important role in the pathogenesis of diseases (Review)

“…The fusiform gyrus (FUS) of the brain is important in facial recognition. Studies have indicated that the expression levels of CAPN3 and other four characteristic genes are abnormal in FUS and that there are related changes in the DNA methylome profiles of these genes ( 111 ). Compared with that of currently used clinical standards, the level of sensitivity of these related methylome profile changes is higher and may effectively predict the prognosis of AD.…”