Down but Not Out: The Consequences of Pretangle Tau in the Locus Coeruleus
Degeneration of locus coeruleus (LC) is an underappreciated hallmark of Alzheimer’s disease (AD). The LC is the main source of norepinephrine (NE) in the forebrain, and its degeneration is highly correlated with cognitive impairment and amyloid-beta (Aβ) and tangle pathology. Hyperphosphorylated tau...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2017/7829507 |
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| author | Termpanit Chalermpalanupap David Weinshenker Jacki M. Rorabaugh |
| author_facet | Termpanit Chalermpalanupap David Weinshenker Jacki M. Rorabaugh |
| author_sort | Termpanit Chalermpalanupap |
| collection | DOAJ |
| description | Degeneration of locus coeruleus (LC) is an underappreciated hallmark of Alzheimer’s disease (AD). The LC is the main source of norepinephrine (NE) in the forebrain, and its degeneration is highly correlated with cognitive impairment and amyloid-beta (Aβ) and tangle pathology. Hyperphosphorylated tau in the LC is among the first detectable AD-like neuropathology in the brain, and while the LC/NE system impacts multiple aspects of AD (e.g., cognition, neuropathology, and neuroinflammation), the functional consequences of hyperphosphorylated tau accrual on LC neurons are not known. Recent evidence suggests that LC neurons accumulate aberrant tau species for decades before frank LC cell body degeneration occurs in AD, suggesting that a therapeutic window exists. In this review, we combine the literature on how pathogenic tau affects forebrain neurons with the known properties and degeneration patterns of LC neurons to synthesize hypotheses on hyperphosphorylated tau-induced dysfunction of LC neurons and the prion-like spread of pretangle tau from the LC to the forebrain. We also propose novel experiments using both in vitro and in vivo models to address the many questions surrounding the impact of hyperphosphorylated tau on LC neurons in AD and its role in disease progression. |
| format | Article |
| id | doaj-art-5abf8a1afaf2473e8c90131e54041429 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-5abf8a1afaf2473e8c90131e540414292025-02-03T05:53:00ZengWileyNeural Plasticity2090-59041687-54432017-01-01201710.1155/2017/78295077829507Down but Not Out: The Consequences of Pretangle Tau in the Locus CoeruleusTermpanit Chalermpalanupap0David Weinshenker1Jacki M. Rorabaugh2Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USADegeneration of locus coeruleus (LC) is an underappreciated hallmark of Alzheimer’s disease (AD). The LC is the main source of norepinephrine (NE) in the forebrain, and its degeneration is highly correlated with cognitive impairment and amyloid-beta (Aβ) and tangle pathology. Hyperphosphorylated tau in the LC is among the first detectable AD-like neuropathology in the brain, and while the LC/NE system impacts multiple aspects of AD (e.g., cognition, neuropathology, and neuroinflammation), the functional consequences of hyperphosphorylated tau accrual on LC neurons are not known. Recent evidence suggests that LC neurons accumulate aberrant tau species for decades before frank LC cell body degeneration occurs in AD, suggesting that a therapeutic window exists. In this review, we combine the literature on how pathogenic tau affects forebrain neurons with the known properties and degeneration patterns of LC neurons to synthesize hypotheses on hyperphosphorylated tau-induced dysfunction of LC neurons and the prion-like spread of pretangle tau from the LC to the forebrain. We also propose novel experiments using both in vitro and in vivo models to address the many questions surrounding the impact of hyperphosphorylated tau on LC neurons in AD and its role in disease progression.http://dx.doi.org/10.1155/2017/7829507 |
| spellingShingle | Termpanit Chalermpalanupap David Weinshenker Jacki M. Rorabaugh Down but Not Out: The Consequences of Pretangle Tau in the Locus Coeruleus Neural Plasticity |
| title | Down but Not Out: The Consequences of Pretangle Tau in the Locus Coeruleus |
| title_full | Down but Not Out: The Consequences of Pretangle Tau in the Locus Coeruleus |
| title_fullStr | Down but Not Out: The Consequences of Pretangle Tau in the Locus Coeruleus |
| title_full_unstemmed | Down but Not Out: The Consequences of Pretangle Tau in the Locus Coeruleus |
| title_short | Down but Not Out: The Consequences of Pretangle Tau in the Locus Coeruleus |
| title_sort | down but not out the consequences of pretangle tau in the locus coeruleus |
| url | http://dx.doi.org/10.1155/2017/7829507 |
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