Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease
Down syndrome (DS, trisomy 21) is characterized by intellectual impairment at birth and Alzheimer’s disease (AD) pathology in middle age. As individuals with DS age, their cognitive functions decline as they develop AD pathology. The susceptibility to degeneration of a subset of neurons, known as ba...
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doaj-09beed709c0a43ce91b3aa786dd19fdb2021-08-05T14:36:01ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-07-011310.3389/fnagi.2021.703876703876Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s DiseaseJose L. Martinez0Jose L. Martinez1Matthew D. Zammit2Matthew D. Zammit3Nicole R. West4Nicole R. West5Bradley T. Christian6Bradley T. Christian7Bradley T. Christian8Anita Bhattacharyya9Anita Bhattacharyya10Cellular and Molecular Biology Graduate Program, University of Wisconsin, Madison, WI, United StatesWaisman Center, University of Wisconsin, Madison, WI, United StatesWaisman Center, University of Wisconsin, Madison, WI, United StatesDepartment of Medical Physics, School of Medicine and Public Health, University of Wisconsin, Madison, WI, United StatesCellular and Molecular Biology Graduate Program, University of Wisconsin, Madison, WI, United StatesWaisman Center, University of Wisconsin, Madison, WI, United StatesWaisman Center, University of Wisconsin, Madison, WI, United StatesDepartment of Medical Physics, School of Medicine and Public Health, University of Wisconsin, Madison, WI, United StatesDepartment of Psychiatry, School of Medicine and Public Health, University of Wisconsin, Madison, WI, United StatesWaisman Center, University of Wisconsin, Madison, WI, United StatesDepartment of Cellular and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, United StatesDown syndrome (DS, trisomy 21) is characterized by intellectual impairment at birth and Alzheimer’s disease (AD) pathology in middle age. As individuals with DS age, their cognitive functions decline as they develop AD pathology. The susceptibility to degeneration of a subset of neurons, known as basal forebrain cholinergic neurons (BFCNs), in DS and AD is a critical link between cognitive impairment and neurodegeneration in both disorders. BFCNs are the primary source of cholinergic innervation to the cerebral cortex and hippocampus, as well as the amygdala. They play a critical role in the processing of information related to cognitive function and are directly engaged in regulating circuits of attention and memory throughout the lifespan. Given the importance of BFCNs in attention and memory, it is not surprising that these neurons contribute to dysfunctional neuronal circuitry in DS and are vulnerable in adults with DS and AD, where their degeneration leads to memory loss and disturbance in language. BFCNs are thus a relevant cell target for therapeutics for both DS and AD but, despite some success, efforts in this area have waned. There are gaps in our knowledge of BFCN vulnerability that preclude our ability to effectively design interventions. Here, we review the role of BFCN function and degeneration in AD and DS and identify under-studied aspects of BFCN biology. The current gaps in BFCN relevant imaging studies, therapeutics, and human models limit our insight into the mechanistic vulnerability of BFCNs in individuals with DS and AD.https://www.frontiersin.org/articles/10.3389/fnagi.2021.703876/fullbasal forebrain cholinergic neuronsdown syndromeAlzheimer’s diseasepluripotent stem cellneurodegeneration |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jose L. Martinez Jose L. Martinez Matthew D. Zammit Matthew D. Zammit Nicole R. West Nicole R. West Bradley T. Christian Bradley T. Christian Bradley T. Christian Anita Bhattacharyya Anita Bhattacharyya |
spellingShingle |
Jose L. Martinez Jose L. Martinez Matthew D. Zammit Matthew D. Zammit Nicole R. West Nicole R. West Bradley T. Christian Bradley T. Christian Bradley T. Christian Anita Bhattacharyya Anita Bhattacharyya Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease Frontiers in Aging Neuroscience basal forebrain cholinergic neurons down syndrome Alzheimer’s disease pluripotent stem cell neurodegeneration |
author_facet |
Jose L. Martinez Jose L. Martinez Matthew D. Zammit Matthew D. Zammit Nicole R. West Nicole R. West Bradley T. Christian Bradley T. Christian Bradley T. Christian Anita Bhattacharyya Anita Bhattacharyya |
author_sort |
Jose L. Martinez |
title |
Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease |
title_short |
Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease |
title_full |
Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease |
title_fullStr |
Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease |
title_full_unstemmed |
Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease |
title_sort |
basal forebrain cholinergic neurons: linking down syndrome and alzheimer’s disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Aging Neuroscience |
issn |
1663-4365 |
publishDate |
2021-07-01 |
description |
Down syndrome (DS, trisomy 21) is characterized by intellectual impairment at birth and Alzheimer’s disease (AD) pathology in middle age. As individuals with DS age, their cognitive functions decline as they develop AD pathology. The susceptibility to degeneration of a subset of neurons, known as basal forebrain cholinergic neurons (BFCNs), in DS and AD is a critical link between cognitive impairment and neurodegeneration in both disorders. BFCNs are the primary source of cholinergic innervation to the cerebral cortex and hippocampus, as well as the amygdala. They play a critical role in the processing of information related to cognitive function and are directly engaged in regulating circuits of attention and memory throughout the lifespan. Given the importance of BFCNs in attention and memory, it is not surprising that these neurons contribute to dysfunctional neuronal circuitry in DS and are vulnerable in adults with DS and AD, where their degeneration leads to memory loss and disturbance in language. BFCNs are thus a relevant cell target for therapeutics for both DS and AD but, despite some success, efforts in this area have waned. There are gaps in our knowledge of BFCN vulnerability that preclude our ability to effectively design interventions. Here, we review the role of BFCN function and degeneration in AD and DS and identify under-studied aspects of BFCN biology. The current gaps in BFCN relevant imaging studies, therapeutics, and human models limit our insight into the mechanistic vulnerability of BFCNs in individuals with DS and AD. |
topic |
basal forebrain cholinergic neurons down syndrome Alzheimer’s disease pluripotent stem cell neurodegeneration |
url |
https://www.frontiersin.org/articles/10.3389/fnagi.2021.703876/full |
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