Waste Clearance in the Brain and Neuroinflammation: A Novel Perspective on Biomarker and Drug Target Discovery in Alzheimer’s Disease
Alzheimer’s disease (AD) is a multifactorial disease with a heterogeneous etiology. The pathology of Alzheimer’s disease is characterized by amyloid-beta and hyperphosphorylated tau, which are necessary for disease progression. Many clinical trials on disease-modifying drugs for AD have failed to in...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/5/919 |
| _version_ | 1797475336804368384 |
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| author | Kazuhiko Uchida |
| author_facet | Kazuhiko Uchida |
| author_sort | Kazuhiko Uchida |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a multifactorial disease with a heterogeneous etiology. The pathology of Alzheimer’s disease is characterized by amyloid-beta and hyperphosphorylated tau, which are necessary for disease progression. Many clinical trials on disease-modifying drugs for AD have failed to indicate their clinical benefits. Recent advances in fundamental research have indicated that neuroinflammation plays an important pathological role in AD. Damage- and pathogen-associated molecular patterns in the brain induce neuroinflammation and inflammasome activation, causing caspase-1-dependent glial and neuronal cell death. These waste products in the brain are eliminated by the glymphatic system via perivascular spaces, the blood-brain barrier, and the blood–cerebrospinal fluid barrier. Age-related vascular dysfunction is associated with an impairment of clearance and barrier functions, leading to neuroinflammation. The proteins involved in waste clearance in the brain and peripheral circulation may be potential biomarkers and drug targets in the early stages of cognitive impairment. This short review focuses on waste clearance dysfunction in AD pathobiology and discusses the improvement of waste clearance as an early intervention in prodromal AD and preclinical stages of dementia. |
| first_indexed | 2024-03-09T20:43:40Z |
| format | Article |
| id | doaj.art-5c096758ca0c4a5c99db683269593073 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:43:40Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-5c096758ca0c4a5c99db6832695930732023-11-23T22:52:15ZengMDPI AGCells2073-44092022-03-0111591910.3390/cells11050919Waste Clearance in the Brain and Neuroinflammation: A Novel Perspective on Biomarker and Drug Target Discovery in Alzheimer’s DiseaseKazuhiko Uchida0Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Ibaraki, JapanAlzheimer’s disease (AD) is a multifactorial disease with a heterogeneous etiology. The pathology of Alzheimer’s disease is characterized by amyloid-beta and hyperphosphorylated tau, which are necessary for disease progression. Many clinical trials on disease-modifying drugs for AD have failed to indicate their clinical benefits. Recent advances in fundamental research have indicated that neuroinflammation plays an important pathological role in AD. Damage- and pathogen-associated molecular patterns in the brain induce neuroinflammation and inflammasome activation, causing caspase-1-dependent glial and neuronal cell death. These waste products in the brain are eliminated by the glymphatic system via perivascular spaces, the blood-brain barrier, and the blood–cerebrospinal fluid barrier. Age-related vascular dysfunction is associated with an impairment of clearance and barrier functions, leading to neuroinflammation. The proteins involved in waste clearance in the brain and peripheral circulation may be potential biomarkers and drug targets in the early stages of cognitive impairment. This short review focuses on waste clearance dysfunction in AD pathobiology and discusses the improvement of waste clearance as an early intervention in prodromal AD and preclinical stages of dementia.https://www.mdpi.com/2073-4409/11/5/919Aβ clearanceblood-brain barrierglymphatic systeminnate immunitymild cognitive impairment |
| spellingShingle | Kazuhiko Uchida Waste Clearance in the Brain and Neuroinflammation: A Novel Perspective on Biomarker and Drug Target Discovery in Alzheimer’s Disease Cells Aβ clearance blood-brain barrier glymphatic system innate immunity mild cognitive impairment |
| title | Waste Clearance in the Brain and Neuroinflammation: A Novel Perspective on Biomarker and Drug Target Discovery in Alzheimer’s Disease |
| title_full | Waste Clearance in the Brain and Neuroinflammation: A Novel Perspective on Biomarker and Drug Target Discovery in Alzheimer’s Disease |
| title_fullStr | Waste Clearance in the Brain and Neuroinflammation: A Novel Perspective on Biomarker and Drug Target Discovery in Alzheimer’s Disease |
| title_full_unstemmed | Waste Clearance in the Brain and Neuroinflammation: A Novel Perspective on Biomarker and Drug Target Discovery in Alzheimer’s Disease |
| title_short | Waste Clearance in the Brain and Neuroinflammation: A Novel Perspective on Biomarker and Drug Target Discovery in Alzheimer’s Disease |
| title_sort | waste clearance in the brain and neuroinflammation a novel perspective on biomarker and drug target discovery in alzheimer s disease |
| topic | Aβ clearance blood-brain barrier glymphatic system innate immunity mild cognitive impairment |
| url | https://www.mdpi.com/2073-4409/11/5/919 |
| work_keys_str_mv | AT kazuhikouchida wasteclearanceinthebrainandneuroinflammationanovelperspectiveonbiomarkeranddrugtargetdiscoveryinalzheimersdisease |