Tau-Reactive Endogenous Antibodies: Origin, Functionality, and Implications for the Pathophysiology of Alzheimer’s Disease
In Alzheimer’s disease (AD), tau pathology manifested by the accumulation of intraneuronal tangles and soluble toxic oligomers emerges as a promising therapeutic target. Multiple anti-tau antibodies inhibiting the formation and propagation of cytotoxic tau or promoting its clearance and degradation...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/7406810 |
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| author | Lenka Hromadkova Saak Victor Ovsepian |
| author_facet | Lenka Hromadkova Saak Victor Ovsepian |
| author_sort | Lenka Hromadkova |
| collection | DOAJ |
| description | In Alzheimer’s disease (AD), tau pathology manifested by the accumulation of intraneuronal tangles and soluble toxic oligomers emerges as a promising therapeutic target. Multiple anti-tau antibodies inhibiting the formation and propagation of cytotoxic tau or promoting its clearance and degradation have been tested in clinical trials, albeit with the inconclusive outcome. Antibodies against tau protein have been documented both in the brain circulatory system and at the periphery, but their origin and role under normal conditions and in AD remain unclear. While it is tempting to assign them a protective role in regulating tau level and removal of toxic variants, the supportive evidence remains sporadic, requiring systematic analysis and critical evaluation. Herein, we review recent data showing the occurrence of tau-reactive antibodies in the brain and peripheral circulation and discuss their origin and significance in tau clearance. Based on the emerging evidence, we cautiously propose that impairments of tau clearance at the periphery by humoral immunity might aggravate the tau pathology in the central nervous system, with implication for the neurodegenerative process of AD. |
| format | Article |
| id | doaj-art-0e39cd4c7f1540bc9dc7be3a257cc175 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-0e39cd4c7f1540bc9dc7be3a257cc1752025-02-03T05:46:00ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/74068107406810Tau-Reactive Endogenous Antibodies: Origin, Functionality, and Implications for the Pathophysiology of Alzheimer’s DiseaseLenka Hromadkova0Saak Victor Ovsepian1National Institute of Mental Health, Klecany 25067, Czech RepublicNational Institute of Mental Health, Klecany 25067, Czech RepublicIn Alzheimer’s disease (AD), tau pathology manifested by the accumulation of intraneuronal tangles and soluble toxic oligomers emerges as a promising therapeutic target. Multiple anti-tau antibodies inhibiting the formation and propagation of cytotoxic tau or promoting its clearance and degradation have been tested in clinical trials, albeit with the inconclusive outcome. Antibodies against tau protein have been documented both in the brain circulatory system and at the periphery, but their origin and role under normal conditions and in AD remain unclear. While it is tempting to assign them a protective role in regulating tau level and removal of toxic variants, the supportive evidence remains sporadic, requiring systematic analysis and critical evaluation. Herein, we review recent data showing the occurrence of tau-reactive antibodies in the brain and peripheral circulation and discuss their origin and significance in tau clearance. Based on the emerging evidence, we cautiously propose that impairments of tau clearance at the periphery by humoral immunity might aggravate the tau pathology in the central nervous system, with implication for the neurodegenerative process of AD.http://dx.doi.org/10.1155/2019/7406810 |
| spellingShingle | Lenka Hromadkova Saak Victor Ovsepian Tau-Reactive Endogenous Antibodies: Origin, Functionality, and Implications for the Pathophysiology of Alzheimer’s Disease Journal of Immunology Research |
| title | Tau-Reactive Endogenous Antibodies: Origin, Functionality, and Implications for the Pathophysiology of Alzheimer’s Disease |
| title_full | Tau-Reactive Endogenous Antibodies: Origin, Functionality, and Implications for the Pathophysiology of Alzheimer’s Disease |
| title_fullStr | Tau-Reactive Endogenous Antibodies: Origin, Functionality, and Implications for the Pathophysiology of Alzheimer’s Disease |
| title_full_unstemmed | Tau-Reactive Endogenous Antibodies: Origin, Functionality, and Implications for the Pathophysiology of Alzheimer’s Disease |
| title_short | Tau-Reactive Endogenous Antibodies: Origin, Functionality, and Implications for the Pathophysiology of Alzheimer’s Disease |
| title_sort | tau reactive endogenous antibodies origin functionality and implications for the pathophysiology of alzheimer s disease |
| url | http://dx.doi.org/10.1155/2019/7406810 |
| work_keys_str_mv | AT lenkahromadkova taureactiveendogenousantibodiesoriginfunctionalityandimplicationsforthepathophysiologyofalzheimersdisease AT saakvictorovsepian taureactiveendogenousantibodiesoriginfunctionalityandimplicationsforthepathophysiologyofalzheimersdisease |