Revolution of Resting-State Functional Neuroimaging Genetics in Alzheimer’s Disease

Chiesa, Patrizia Andrea; Cavedo, Enrica; Lista, Simone; Thompson, Paul M.; Hampel, Harald

doi:10.1016/j.tins.2017.06.002

Cited by 34 publications

(31 citation statements)

References 85 publications

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“…Therefore, basal forebrain functional alterations may be a promising candidate for an early preclinical biomarker of AD and a potentially useful functional outcome in of both factors: the APOE ´4 allele showed stronger correlation between the global brain amyloid deposit and the PBF functional dynamics in occipital regions and in the thalamus. We provided further evidence that the APOE ´4 allele is linked to abnormal amyloid-b aggregation (41)(42)(43)(44) and leads to differences in the brain functional organization in cognitively intact individuals (2). This result supports the hypothesis of different binding characteristics of the APOE ´4 isoform with amyloid-b (45).…”

Section: Role Of Apoe Genotype and Sex On The Basal Forebrain Rsfc-susupporting

confidence: 81%

Relationship between Basal Forebrain Resting-State Functional Connectivity and Brain Amyloid-β Deposition in Cognitively Intact Older Adults with Subjective Memory Complaints

Chiesa¹,

Cavedo²,

Grothe³

et al. 2019

Radiology

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Section: Role Of Apoe Genotype and Sex On The Basal Forebrain Rsfc-susupporting

confidence: 81%

Relationship between Basal Forebrain Resting-State Functional Connectivity and Brain Amyloid-β Deposition in Cognitively Intact Older Adults with Subjective Memory Complaints

Chiesa¹,

Cavedo²,

Grothe³

et al. 2019

Radiology

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“…Our findings of the different effects of APP and PS1 mutation on this circuit expanded our understanding of this potential biomarker. Both APP and PS1 mutation can cause direct elevation of the Aβ level via alterations of their encoding proteins and, as a result, affect synaptic plasticity [40,63]. They also affect other functions of their encoding proteins, such as axonal transport, lysosome PS1 and APP mutation subjects without symptoms were compared with the control group, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, most of the above imaging findings in FAD have involved mutation carriers of various genes, while not looked at the effect of specific gene. Imaging studies have shown gene-or mutation-specific effect on brain structure [38,39] and function [40] in Alzheimer's disease, but the gene-specific effect on the frontostriatal and hippocampus-PCC neural circuits remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

Effects of gene mutation and disease progression on representative neural circuits in familial Alzheimer’s disease

et al. 2020

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Background: Although structural and functional changes of the striatum and hippocampus are present in familial Alzheimer's disease, little is known about the effects of specific gene mutation or disease progression on their related neural circuits. This study was to evaluate the effects of known pathogenic gene mutation and disease progression on the striatum-and hippocampus-related neural circuits, including frontostriatal and hippocampusposterior cingulate cortex (PCC) pathways. Methods: A total of 102 healthy mutation non-carriers, 40 presymptomatic mutation carriers (PMC), and 30 symptomatic mutation carriers (SMC) of amyloid precursor protein (APP), presenilin 1 (PS1), or presenilin 2 gene, with T1 structural MRI, diffusion tensor imaging, and resting-state functional MRI were included. Representative neural circuits and their key nodes were obtained, including bilateral caudate-rostral middle frontal gyrus (rMFG), putamen-rMFG, and hippocampus-PCC. Volumes, diffusion indices, and functional connectivity of circuits were compared between groups and correlated with neuropsychological and clinical measures. Results: In PMC, APP gene mutation carriers showed impaired diffusion indices of caudate-rMFG and putamen-rMFG circuits; PS1 gene mutation carriers showed increased fiber numbers of putamen-rMFG circuit. SMC showed increased diffusivity of the left hippocampus-PCC circuit and volume reduction of all regions as compared with PMC. Imaging measures especially axial diffusivity of the representative circuits were correlated with neuropsychological measures. Conclusions: APP and PS1 gene mutations affect frontostriatal circuits in a different manner in familial Alzheimer's disease; disease progression primarily affects the structure of hippocampus-PCC circuit. The structural connectivity of both frontostriatal and hippocampus-PCC circuits is associated with general cognitive function. Such findings may provide further information about the imaging biomarkers for early identification and prognosis of familial Alzheimer's disease, and pave the way for early diagnosis, gene-or circuit-targeted treatment, and even prevention.

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“…In this regard, several potential biological markers have been identified across the full spectrum of AD, from preclinical to prodromal to clinical stages [35–41]. This includes different categories, as follows: 1) neurogenetics/neuroepigenetics markers [42–45], 2) neurochemistry markers [4, 46–48], including both cerebrospinal fluid (CSF) [49–55] and blood (plasma/serum) markers [56–63], 3) markers derived from structural/functional/metabolic neuroimaging [64–68], and 4) neurophysiology/neurodynamic markers [69]. Moreover, opinions of regulatory agencies and industry stakeholders in AD biomarker discovery area are regularly in discussion and development [70, 71].…”

Section: The Precision Neurology Paradigm In Alzheimer’s Diseasementioning

confidence: 99%

“…The tailoring of therapeutics could benefit from associations between biomarkers and the presence of the disease pathophysiology. Given the variability that is present in AD patients and MCI subjects, the ICN-based biomarkers and their relation to genetic profiles [68] may be able to provide an improved systems biology characterization of brain function. The use of ICNs for tailoring therapeutics still needs considerable development work, and there is currently only limited work on the effects of an AD-related drug on ICNs [307].…”

Section: Contribution and Role Of Functional Magnetic Resonance Imagimentioning

confidence: 99%

Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology

Hampel

Toschi

Babiloni

et al. 2018

JAD

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126

113

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The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an “omics”-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer’s disease (AD). The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group “Alzheimer Precision Medicine” (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development towards breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND.

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Revolution of Resting-State Functional Neuroimaging Genetics in Alzheimer’s Disease

Cited by 34 publications

References 85 publications

Relationship between Basal Forebrain Resting-State Functional Connectivity and Brain Amyloid-β Deposition in Cognitively Intact Older Adults with Subjective Memory Complaints

Relationship between Basal Forebrain Resting-State Functional Connectivity and Brain Amyloid-β Deposition in Cognitively Intact Older Adults with Subjective Memory Complaints

Effects of gene mutation and disease progression on representative neural circuits in familial Alzheimer’s disease

Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology

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