Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer's disease
| Autor: | Liana G. Apostolova, Evan Y. Zhao, Tina Bilousova, Bruce Teter, Qiu-Lan Ma, Mary Jo LaDu, Edmond Teng, Mir Ahamed Hossain, Karen H. Gylys, Xiaohong Zuo, Sally A. Frautschy, Gregory M. Cole, Mychica Jones, Cansheng Zhu |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Male Aging Neurodegenerative Alzheimer's Disease Mice 0302 clinical medicine 80 and over 2.1 Biological and endogenous factors Aetiology Cognitive decline EFAD mice Aged 80 and over Mice Knockout β-amyloid Chemistry beta-amyloid Neurodegeneration Glutamate receptor Brain C-Reactive Protein Neurology Neurological Excitatory postsynaptic potential Biomarker (medicine) Female Neuronal pentraxin 1 Alzheimer's disease APOE medicine.medical_specialty Knockout Clinical Sciences Nerve Tissue Proteins Article lcsh:RC321-571 03 medical and health sciences Alzheimer Disease Internal medicine Acquired Cognitive Impairment medicine Animals Humans Plasma biomarkers lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Aged Neurology & Neurosurgery Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) medicine.disease MCI Brain Disorders 030104 developmental biology Endocrinology Synaptic plasticity Synapses Dementia 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | Neurobiol Dis Neurobiology of Disease, Vol 114, Iss, Pp 120-128 (2018) |
| Popis: | Synaptic neurodegeneration is thought to be an early event initiated by soluble β-amyloid (Aβ) aggregates that closely correlates with cognitive decline in Alzheimer disease (AD). Apolipoprotein e4 (APOE4) is the most common genetic risk factor for both familial AD (FAD) and sporadic AD; it accelerates Aβ aggregation and selectively impairs glutamate receptor function and synaptic plasticity. However, its molecular mechanisms remain elusive and these synaptic deficits are difficult to monitor. AD- and APOE4-dependent plasma biomarkers have been proposed, but synapse-related plasma biomarkers are lacking. We evaluated neuronal pentraxin 1 (NP1), a potential CNS-derived plasma biomarker of excitatory synaptic pathology. NP1 is preferentially expressed in brain and involved in glutamate receptor internalization. NP1 is secreted presynaptically induced by Aβ oligomers, and implicated in excitatory synaptic and mitochondrial deficits. Levels of NP1 and its fragments were increased in a correlated fashion in both brain and plasma of 7–8 month-old E4FAD mice relative to E3FAD mice. NP1 was also found in exosome preparations and reduced by dietary DHA supplementation. Plasma NP1 was higher in E4FAD+ (APOE4+/+/FAD+/−) relative to E4FAD- (non-carrier; APOE4+/+/FAD−/−) mice, suggesting NP1 is modulated by Aβ expression. Finally, relative to normal elderly, plasma NP1 was also elevated in patients with mild cognitive impairment (MCI) and elevated further in the subset who progressed to early-stage AD. In those patients, there was a trend towards increased NP1 levels in APOE4 carriers relative to non-carriers. These findings indicate that NP1 may represent a potential synapse-derived plasma biomarker relevant to early alterations in excitatory synapses in MCI and early-stage AD. |
| Databáze: | OpenAIRE |
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