A review of brain imaging biomarker genomics in Alzheimer’s disease: implementation and perspectives

Li, Lanlan; Yu, Xianfeng; Sheng, Can; Jiang, Xueyan; Zhang, Qi; Han, Ying; Jiang, Jiehui

doi:10.1186/s40035-022-00315-z

Cited by 11 publications

(5 citation statements)

References 189 publications

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“…In recent years, GWAS based on neuroimaging or cerebrospinal fluid (CSF) Aβ and tau levels has been conducted. Although in its initial stage, it has identified vital genes associated with Aβ and tau ( Li et al, 2022 ). Ramanan et al conducted the first neuroimaging GWAS by integrating positron emission tomography (PET) phenotypes with genetic data, confirming the association of APOE and BCHE with Aβ burden ( Ramanan et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study in Alzheimer’s disease: a bibliometric and visualization analysis

Zhang,

Wang,

Zhang

et al. 2023

Front. Aging Neurosci.

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BackgroundThousands of research studies concerning genome-wide association studies (GWAS) in Alzheimer’s disease (AD) have been published in the last decades. However, a comprehensive understanding of the current research status and future development trends of GWAS in AD have not been clearly shown. In this study, we tried to gain a systematic overview of GWAS in AD by bibliometric and visualization analysis.MethodsThe literature search terms are: (“genome-wide analysis” or “genome-wide association study” or “whole-genome analysis”) AND (“Alzheimer’s Disease” or “Alzheimer Disease”). Relevant publications were extracted from the Web of Science Core Collection (WoSCC) database. Collected data were further analyzed using VOSviewer, CiteSpace and R package Bibliometrix. The countries, institutions, authors and scholar collaborations were investigated. The co-citation analysis of publications was visualized. In addition, research hotspots and fronts were examined.ResultsA total of 1,350 publications with 59,818 citations were identified. The number of publications and citations presented a significant rising trend since 2013. The United States was the leading country with an overwhelming number of publications (775) and citations (42,237). The University of Washington and Harvard University were the most prolific institutions with 101 publications each. Bennett DA was the most influential researcher with the highest local H-index. Neurobiology of Aging was the journal with the highest number of publications. Aβ, tau, immunity, microglia and DNA methylation were research hotspots. Disease and causal variants were research fronts.ConclusionThe most frequently studied AD pathogenesis and research hotspots are (1) Aβ and tau, (2) immunity and microglia, with TREM2 as a potential immunotherapy target, and (3) DNA methylation. The research fronts are (1) looking for genetic similarities between AD and other neurological diseases and syndromes, and (2) searching for causal variants of AD. These hotspots suggest noteworthy directions for future studies on AD pathogenesis and genetics, in which basic research regarding immunity is promising for clinical conversion. The current under-researched directions are (1) GWAS in AD biomarkers based on large sample sizes, (2) studies of causal variants of AD, and (3) GWAS in AD based on non-European populations, which need to be strengthened in the future.

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Section: Discussionmentioning

confidence: 99%

Genome-wide association study in Alzheimer’s disease: a bibliometric and visualization analysis

Zhang,

Wang,

Zhang

et al. 2023

Front. Aging Neurosci.

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“…Thus, exploring early diagnostic biomarkers to detect patients with MCI from aging population is urgently needed. In the past decades, researchers have been focusing on exploring imaging, cerebrospinal fluid (CSF) and blood biomarkers for early diagnosis of AD 22–26 . In fact, stool is more accessible and noninvasive sample source compared with above samples.…”

Section: Discussionmentioning

confidence: 99%

“…In the past decades, researchers have been focusing on exploring imaging, cerebrospinal fluid (CSF) and blood biomarkers for early diagnosis of AD. 22 , 23 , 24 , 25 , 26 In fact, stool is more accessible and noninvasive sample source compared with above samples. In recent years, as the brain–gut axis plays a prominent role in the pathogenesis of neurodegenerative diseases, 7 , 8 , 9 , 27 the expression level of gut microbiota in the progress of neurodegenerative diseases such as AD and PD have been examined.…”

Section: Discussionmentioning

confidence: 99%

Early changes of fecal short‐chain fatty acid levels in patients with mild cognitive impairments

Gao

et al. 2023

CNS Neurosci Ther

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AimsTo compare the fecal levels of short‐chain fatty acids (SCFAs) in patients with mild cognitive impairment (MCI) and normal controls (NCs) and to examine whether fecal SCFAs could be used as the biomarker for the identification of patients with MCI. To examine the relationship between fecal SCFAs and amyloid‐β (Aβ) deposition in the brain.MethodsA cohort of 32 MCI patients, 23 Parkinson's disease (PD) patients, and 27 NC were recruited in our study. Fecal levels of SCFAs were measured using chromatography and mass spectrometry. Disease duration, ApoE genotype, body mass index, constipation, and diabetes were evaluated. To assess cognitive impairment, we used the Mini‐Mental Status Examination (MMSE). To assess brain atrophy, the degree of medial temporal atrophy (MTA score, Grade 0–4) was measured by structural MRI. Aβ positron emission tomography with 18F‐florbetapir (FBP) was performed in seven MCI patients at the time of stool sampling and in 28 MCI patients at an average of 12.3 ± 0.4 months from the time of stool sampling to detect and quantify Aβ deposition in the brain.ResultsCompared with NC, MCI patients had significantly lower fecal levels of acetic acid, butyric acid, and caproic acid. Among fecal SCFAs, acetic acid performed the best in discriminating MCI from NC, achieved an AUC of 0.752 (p = 0.001, 95% CI: 0.628–0.876), specificity of 66.7%, and sensitivity of 75%. By combining fecal levels of acetic acid, butyric acid, and caproic acid, the diagnostic specificity was significantly improved, reaching 88.9%. To better verify the diagnostic performance of SCFAs, we randomly assigned 60% of participants into training dataset and 40% into testing dataset. Only acetic acid showed significantly difference between these two groups in the training dataset. Based on the fecal levels of acetic acid, we achieved the ROC curve. Next, the ROC curve was evaluated in the independent test data and 61.5% (8 in 13) of patients with MCI, and 72.7% (8 in 11) of NC could be identified correctly. Subgroup analysis showed that reduced fecal SCFAs in MCI group were negatively associated with Aβ deposition in cognition‐related brain regions.ConclusionReductions in fecal SCFAs were observed in patients with MCI compared with NC. Reduced fecal SCFAs were negatively associated with Aβ deposition in cognition‐related brain regions in MCI group. Our findings suggest that gut metabolite SCFAs have the potential to serve as early diagnostic biomarkers for distinguishing patients with MCI from NC and could serve as potential targets for preventing AD.

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“… 126 Deep learning models that combine neuroimaging and genomics data are in early stages in diagnosis and prediction of AD. 127 , 128 Pending necessary and comprehensive replication studies, these artificial intelligence‐derived models can potentially develop target‐specific therapeutics for personalized medicine.…”

Section: The Heart Of the Problem: Atherosclerosis Versus Arterioscle...mentioning

confidence: 99%

Cardiovascular Disease and Alzheimer's Disease: The Heart–Brain Axis

Saeed,

Lopez,

Cohen

et al. 2023

JAHA

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Cardiovascular disease (CVD) remains one of the leading causes of morbidity and mortality in aging adults across the United States. Prior studies indicate that the presence of atherosclerosis, the pathogenic basis of CVD, is linked with dementias. Alzheimer's disease (AD) and AD‐related dementias are a major public health challenge in the United States. Recent studies indicate that ≈3.7 million Americans ≥65 years of age had clinical AD in 2017, with projected increases to 9.3 million by 2060. Treatment options for AD remain limited. Development of disease‐modifying therapies are challenging due, in part, to the long preclinical window of AD. The preclinical incubation period of AD starts in midlife, providing a critical window for identification and optimization of AD risk factors. Studies link AD with CVD risk factors such as hypertension, inflammation, and dyslipidemia. Both AD and CVD are progressive diseases with decades‐long development periods. CVD can clinically manifest several years earlier than AD, making CVD and its risk factors a potential predictor of future AD. The current review focuses on the state of literature on molecular and metabolic pathways modulating the heart–brain axis underlying the potential association of midlife CVD risk factors and their effect on AD and related dementias. Further, we explore potential CVD/dementia preventive strategies during the window of opportunity in midlife and the future of research in the field in the multiomics and novel biomarker use era.

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A review of brain imaging biomarker genomics in Alzheimer’s disease: implementation and perspectives

Cited by 11 publications

References 189 publications

Genome-wide association study in Alzheimer’s disease: a bibliometric and visualization analysis

Genome-wide association study in Alzheimer’s disease: a bibliometric and visualization analysis

Early changes of fecal short‐chain fatty acid levels in patients with mild cognitive impairments

Cardiovascular Disease and Alzheimer's Disease: The Heart–Brain Axis

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