Inhibitory Neural Network’s Impairments at Hippocampal CA1 LTP in an Aged Transgenic Mouse Model of Alzheimer’s Disease

Seo, Hyeon Jeong; Park, Jung Eun; Choi, Seong-Min; Kim, Taekyoung; Cho, Soo Hyun; Lee, Kyung-Hwa; Song, Woo Keun; Song, Jeong Sup; Jeong, Han-Seong; Kim, Dong Hyun; Kim, Byeong C.

doi:10.3390/ijms22020698

Cited by 14 publications

(4 citation statements)

References 50 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 55 , 56 In addition, Alzheimer’s disease is also characterized by the pathological deposition of amyloid-β peptides in the HIPPO. 57 These lines of evidence support that the HIPPO may be an important and promising brain region for Alzheimer treatment.…”

Section: Discussionmentioning

confidence: 84%

Identification of region-specific splicing QTLs in human hippocampal tissue and its distinctive role in brain disorders

Li,

Zhao,

Kong

et al. 2023

iScience

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 84%

Identification of region-specific splicing QTLs in human hippocampal tissue and its distinctive role in brain disorders

Li,

Zhao,

Kong

et al. 2023

iScience

View full text Add to dashboard Cite

“…In an AD mouse model, NRG1 treatment prevented Aβ-induced impairment of long-term potentiation in hippocampal slices via its receptor ErbB4 (50).Conversely, other experimental works have suggested a negative effect of the NRG1-ErbB4 signaling in AD. Perfusion of NRG1 in hippocampus decreased LTP in AD mice model as well as in control mice (51). Further understandings of NRG1 responseupon amyloid pathology will allow to specify the exact synaptic eventsassociated with CSF and plasma NRG1 modi cations observed in AD patients.…”

Section: Discussionmentioning

confidence: 96%

Plasma Neuregulin 1 as a Synaptic Biomarker in Alzheimer’s Disease.

Vrillon

Mouton‐Liger

Martinet

et al. 2022

Preprint

View full text Add to dashboard Cite

Background:Synaptic dysfunction is an early core feature of Alzheimer’s disease (AD), closely associatedwith cognitive symptoms. Neuregulin 1 (NRG1) is a growth and differentiation factor with a key role in the development and maintenance of synaptic transmission. Previous reports have shown that changes in cerebrospinal fluid (CSF) NRG1 concentrationare associated with cognitive status and biomarker evidence of AD pathology. Plasma biomarkers reflecting synaptic impairment would be of great clinical interest.Objective: To measure plasma NRG1 concentration in AD patientsin comparison with other neurodegenerative disorders and neurological controls (NC)and to study its association with cerebrospinal fluid (CSF) core AD and synaptic biomarkers.Methods: This retrospective study enrolled 127 participants including patients with AD at mild cognitive impairment stage (AD-MCI, n=27) and at dementia stage (n=35), non-AD dementia (n=26, Aβ-negative), non-AD MCI (n=19) and neurological controls (n=20). Plasma and CSF NRG1, as well as CSF core AD biomarkers (Aβ 42/Aβ 40 ratio, phospho-tau and total tau), were measured using ELISA. CSF synaptic markers were measured using ELISA for GAP-43 and neurogranin and through immunoprecipitation mass spectrometry for SNAP-25. Results: Plasma NRG1 concentration was higher in AD-MCI and AD dementia patients compared with neurological controls (respectively P=0.005 and P<0.001). Plasma NRG1 differentiated AD MCI patients from neurological controls with an area under the curve of 88.3%, and AD dementia patients from NC with an area under the curve of 87.3%. Plasma NRG1 correlated with CSF NRG1 (β=0.372, P=0.0056, adjusted on age and sex). Plasma NRG1 was associated with AD CSF core biomarkers in the whole cohort and in Aβ-positive patients (β=-0.197- 0.423). Plasma NRG1 correlated with CSF GAP-43, neurogranin and SNAP-25 (β=0.278-0.355). Plasma NRG1 concentration correlated inversely with MMSE in the whole cohort and in Aβ-positive patients (all, β=-0.188, P=0.038; Aβ+: β=-0.255, P=0.038).Conclusion: Plasma NRG1concentration is increased in AD patients and correlates with CSF core AD and synaptic biomarkers, and cognitive status. Thus, plasma NRG1 is a promising non-invasive biomarker to monitor synaptic impairment in AD.

show abstract

“…Conversely, other experimental works have suggested a negative effect of the NRG1-ErbB4 signaling in AD. Perfusion of NRG1 in the hippocampus decreased LTP in the AD mouse model as well as in control mice [ 59 ]. Further understandings of NRG1 response upon amyloid pathology will allow to specify the exact synaptic events associated with CSF and plasma NRG1 modifications observed in AD patients.…”

Section: Discussionmentioning

confidence: 99%

Plasma neuregulin 1 as a synaptic biomarker in Alzheimer’s disease: a discovery cohort study

et al. 2022

View full text Add to dashboard Cite

Background Synaptic dysfunction is an early core feature of Alzheimer’s disease (AD), closely associated with cognitive symptoms. Neuregulin 1 (NRG1) is a growth and differentiation factor with a key role in the development and maintenance of synaptic transmission. Previous reports have shown that changes in cerebrospinal fluid (CSF) NRG1 concentration are associated with cognitive status and biomarker evidence of AD pathology. Plasma biomarkers reflecting synaptic impairment would be of great clinical interest. Objective To measure plasma NRG1 concentration in AD patients in comparison with other neurodegenerative disorders and neurological controls (NC) and to study its association with cerebrospinal fluid (CSF) core AD and synaptic biomarkers. Methods This retrospective study enrolled 127 participants including patients with AD at mild cognitive impairment stage (AD-MCI, n = 27) and at dementia stage (n = 35), non-AD dementia (n = 26, Aβ-negative), non-AD MCI (n = 19), and neurological controls (n=20). Plasma and CSF NRG1, as well as CSF core AD biomarkers (Aβ 42/Aβ 40 ratio, phospho-tau, and total tau), were measured using ELISA. CSF synaptic markers were measured using ELISA for GAP-43 and neurogranin and through immunoprecipitation mass spectrometry for SNAP-25. Results Plasma NRG1 concentration was higher in AD-MCI and AD dementia patients compared with neurological controls (respectively P = 0.005 and P < 0.001). Plasma NRG1 differentiated AD MCI patients from neurological controls with an area under the curve of 88.3%, and AD dementia patients from NC with an area under the curve of 87.3%. Plasma NRG1 correlated with CSF NRG1 (β = 0.372, P = 0.0056, adjusted on age and sex). Plasma NRG1 was associated with AD CSF core biomarkers in the whole cohort and in Aβ-positive patients (β = −0.197–0.423). Plasma NRG1 correlated with CSF GAP-43, neurogranin, and SNAP-25 (β = 0.278–0.355). Plasma NRG1 concentration correlated inversely with MMSE in the whole cohort and in Aβ-positive patients (all, β = −0.188, P = 0.038; Aβ+: β = −0.255, P = 0.038). Conclusion Plasma NRG1 concentration is increased in AD patients and correlates with CSF core AD and synaptic biomarkers and cognitive status. Thus, plasma NRG1 is a promising non-invasive biomarker to monitor synaptic impairment in AD.

show abstract

Inhibitory Neural Network’s Impairments at Hippocampal CA1 LTP in an Aged Transgenic Mouse Model of Alzheimer’s Disease

Cited by 14 publications

References 50 publications

Identification of region-specific splicing QTLs in human hippocampal tissue and its distinctive role in brain disorders

Identification of region-specific splicing QTLs in human hippocampal tissue and its distinctive role in brain disorders

Plasma Neuregulin 1 as a Synaptic Biomarker in Alzheimer’s Disease.

Plasma neuregulin 1 as a synaptic biomarker in Alzheimer’s disease: a discovery cohort study

Contact Info

Product

Resources

About