Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer’s Disease
The clinical features and pathophysiology of neuropsychiatric symptoms (NPSs) in dementia have been extensively studied. However, the genetic architecture and underlying neurobiological mechanisms of NPSs at preclinical stages of cognitive decline and Alzheimer’s disease (AD) remain largely unknown....
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/5/2645 |
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| author | Efthalia Angelopoulou Christos Koros Alexandros Hatzimanolis Leonidas Stefanis Nikolaos Scarmeas Sokratis G. Papageorgiou |
| author_facet | Efthalia Angelopoulou Christos Koros Alexandros Hatzimanolis Leonidas Stefanis Nikolaos Scarmeas Sokratis G. Papageorgiou |
| author_sort | Efthalia Angelopoulou |
| collection | DOAJ |
| description | The clinical features and pathophysiology of neuropsychiatric symptoms (NPSs) in dementia have been extensively studied. However, the genetic architecture and underlying neurobiological mechanisms of NPSs at preclinical stages of cognitive decline and Alzheimer’s disease (AD) remain largely unknown. Mild behavioral impairment (MBI) represents an at-risk state for incident cognitive impairment and is defined by the emergence of persistent NPSs among non-demented individuals in later life. These NPSs include affective dysregulation, decreased motivation, impulse dyscontrol, abnormal perception and thought content, and social inappropriateness. Accumulating evidence has recently begun to shed more light on the genetic background of MBI, focusing on its potential association with genetic factors related to AD. The Apolipoprotein E (APOE) genotype and the MS4A locus have been associated with affective dysregulation, ZCWPW1 with social inappropriateness and psychosis, BIN1 and EPHA1 with psychosis, and NME8 with apathy. The association between MBI and polygenic risk scores (PRSs) in terms of AD dementia has been also explored. Potential implicated mechanisms include neuroinflammation, synaptic dysfunction, epigenetic modifications, oxidative stress responses, proteosomal impairment, and abnormal immune responses. In this review, we summarize and critically discuss the available evidence on the genetic background of MBI with an emphasis on AD, aiming to gain insights into the potential underlying neurobiological mechanisms, which till now remain largely unexplored. In addition, we propose future areas of research in this emerging field, with the aim to better understand the molecular pathophysiology of MBI and its genetic links with cognitive decline. |
| first_indexed | 2024-04-25T00:29:14Z |
| format | Article |
| id | doaj.art-a2a5359e14bb4d9aaa8a7f5585290df6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-25T00:29:14Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a2a5359e14bb4d9aaa8a7f5585290df62024-03-12T16:45:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01255264510.3390/ijms25052645Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer’s DiseaseEfthalia Angelopoulou0Christos Koros1Alexandros Hatzimanolis2Leonidas Stefanis3Nikolaos Scarmeas4Sokratis G. Papageorgiou51st Department of Neurology, Aiginition University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece1st Department of Neurology, Aiginition University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece1st Department of Psychiatry, Aiginition University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece1st Department of Neurology, Aiginition University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece1st Department of Neurology, Aiginition University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece1st Department of Neurology, Aiginition University Hospital, National and Kapodistrian University of Athens, 11528 Athens, GreeceThe clinical features and pathophysiology of neuropsychiatric symptoms (NPSs) in dementia have been extensively studied. However, the genetic architecture and underlying neurobiological mechanisms of NPSs at preclinical stages of cognitive decline and Alzheimer’s disease (AD) remain largely unknown. Mild behavioral impairment (MBI) represents an at-risk state for incident cognitive impairment and is defined by the emergence of persistent NPSs among non-demented individuals in later life. These NPSs include affective dysregulation, decreased motivation, impulse dyscontrol, abnormal perception and thought content, and social inappropriateness. Accumulating evidence has recently begun to shed more light on the genetic background of MBI, focusing on its potential association with genetic factors related to AD. The Apolipoprotein E (APOE) genotype and the MS4A locus have been associated with affective dysregulation, ZCWPW1 with social inappropriateness and psychosis, BIN1 and EPHA1 with psychosis, and NME8 with apathy. The association between MBI and polygenic risk scores (PRSs) in terms of AD dementia has been also explored. Potential implicated mechanisms include neuroinflammation, synaptic dysfunction, epigenetic modifications, oxidative stress responses, proteosomal impairment, and abnormal immune responses. In this review, we summarize and critically discuss the available evidence on the genetic background of MBI with an emphasis on AD, aiming to gain insights into the potential underlying neurobiological mechanisms, which till now remain largely unexplored. In addition, we propose future areas of research in this emerging field, with the aim to better understand the molecular pathophysiology of MBI and its genetic links with cognitive decline.https://www.mdpi.com/1422-0067/25/5/2645mild behavioral impairmentdementiaAlzheimer’s diseasepolygenic risk scoresSNPsgenetic variation |
| spellingShingle | Efthalia Angelopoulou Christos Koros Alexandros Hatzimanolis Leonidas Stefanis Nikolaos Scarmeas Sokratis G. Papageorgiou Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer’s Disease International Journal of Molecular Sciences mild behavioral impairment dementia Alzheimer’s disease polygenic risk scores SNPs genetic variation |
| title | Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer’s Disease |
| title_full | Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer’s Disease |
| title_fullStr | Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer’s Disease |
| title_full_unstemmed | Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer’s Disease |
| title_short | Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer’s Disease |
| title_sort | exploring the genetic landscape of mild behavioral impairment as an early marker of cognitive decline an updated review focusing on alzheimer s disease |
| topic | mild behavioral impairment dementia Alzheimer’s disease polygenic risk scores SNPs genetic variation |
| url | https://www.mdpi.com/1422-0067/25/5/2645 |
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