Concordant and Discordant Cerebrospinal Fluid and Plasma Cytokine and Chemokine Responses in Mild Cognitive Impairment and Early-Stage Alzheimer’s Disease
Neuroinflammation may be a pathogenic mediator and biomarker of neurodegeneration at the boundary between mild cognitive impairment (MCI) and early-stage Alzheimer’s disease (AD). Whether neuroinflammatory processes are endogenous to the central nervous system (CNS) or originate from systemic (perip...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/11/9/2394 |
| _version_ | 1797581157851725824 |
|---|---|
| author | Suzanne M. de la Monte Ming Tong Andrew J. Hapel |
| author_facet | Suzanne M. de la Monte Ming Tong Andrew J. Hapel |
| author_sort | Suzanne M. de la Monte |
| collection | DOAJ |
| description | Neuroinflammation may be a pathogenic mediator and biomarker of neurodegeneration at the boundary between mild cognitive impairment (MCI) and early-stage Alzheimer’s disease (AD). Whether neuroinflammatory processes are endogenous to the central nervous system (CNS) or originate from systemic (peripheral blood) sources could impact strategies for therapeutic intervention. To address this issue, we measured cytokine and chemokine immunoreactivities in simultaneously obtained lumbar puncture cerebrospinal fluid (CSF) and serum samples from 39 patients including 18 with MCI or early AD and 21 normal controls using a 27-plex XMAP bead-based enzyme-linked immunosorbent assay (ELISA). The MCI/AD combined group had significant (<i>p</i> < 0.05 or better) or statistically trend-wise (0.05 ≤ <i>p</i> ≤ 0.10) concordant increases in CSF and serum IL-4, IL-5, IL-9, IL-13, and TNF-α and reductions in GM-CSF, b-FGF, IL-6, IP-10, and MCP-1; CSF-only increases in IFN-y and IL-7 and reductions in VEGF and IL-12p70; serum-only increases in IL-1β, MIP-1α, and eotaxin and reductions in G-CSF, IL-2, IL-8 and IL-15; and discordant CSF–serum responses with reduced CSF and increased serum PDGF-bb, IL-17a, and RANTES. The results demonstrate simultaneously parallel mixed but modestly greater pro-inflammatory compared to anti-inflammatory or neuroprotective responses in CSF and serum. In addition, the findings show evidence that several cytokines and chemokines are selectively altered in MCI/AD CSF, likely corresponding to distinct neuroinflammatory responses unrelated to systemic pathologies. The aggregate results suggest that early management of MCI/AD neuroinflammation should include both anti-inflammatory and pro-neuroprotective strategies to help prevent disease progression. |
| first_indexed | 2024-03-10T23:00:09Z |
| format | Article |
| id | doaj.art-4b2c490ac7e7497e82df6b4411c4f6fe |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T23:00:09Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-4b2c490ac7e7497e82df6b4411c4f6fe2023-11-19T09:40:42ZengMDPI AGBiomedicines2227-90592023-08-01119239410.3390/biomedicines11092394Concordant and Discordant Cerebrospinal Fluid and Plasma Cytokine and Chemokine Responses in Mild Cognitive Impairment and Early-Stage Alzheimer’s DiseaseSuzanne M. de la Monte0Ming Tong1Andrew J. Hapel2Departments of Pathology (Neuropathology), Neurology, and Neurosurgery, Rhode Island Hospital, The Alpert Medical School of Brown University, Providence, RI 02903, USADepartment of Medicine, Rhode Island Hospital, The Alpert Medical School of Brown University, Providence, RI 02903, USADepartment of Genome Biology, John Curtin School of Medical Research, Australian National University, Canberra 2601, AustraliaNeuroinflammation may be a pathogenic mediator and biomarker of neurodegeneration at the boundary between mild cognitive impairment (MCI) and early-stage Alzheimer’s disease (AD). Whether neuroinflammatory processes are endogenous to the central nervous system (CNS) or originate from systemic (peripheral blood) sources could impact strategies for therapeutic intervention. To address this issue, we measured cytokine and chemokine immunoreactivities in simultaneously obtained lumbar puncture cerebrospinal fluid (CSF) and serum samples from 39 patients including 18 with MCI or early AD and 21 normal controls using a 27-plex XMAP bead-based enzyme-linked immunosorbent assay (ELISA). The MCI/AD combined group had significant (<i>p</i> < 0.05 or better) or statistically trend-wise (0.05 ≤ <i>p</i> ≤ 0.10) concordant increases in CSF and serum IL-4, IL-5, IL-9, IL-13, and TNF-α and reductions in GM-CSF, b-FGF, IL-6, IP-10, and MCP-1; CSF-only increases in IFN-y and IL-7 and reductions in VEGF and IL-12p70; serum-only increases in IL-1β, MIP-1α, and eotaxin and reductions in G-CSF, IL-2, IL-8 and IL-15; and discordant CSF–serum responses with reduced CSF and increased serum PDGF-bb, IL-17a, and RANTES. The results demonstrate simultaneously parallel mixed but modestly greater pro-inflammatory compared to anti-inflammatory or neuroprotective responses in CSF and serum. In addition, the findings show evidence that several cytokines and chemokines are selectively altered in MCI/AD CSF, likely corresponding to distinct neuroinflammatory responses unrelated to systemic pathologies. The aggregate results suggest that early management of MCI/AD neuroinflammation should include both anti-inflammatory and pro-neuroprotective strategies to help prevent disease progression.https://www.mdpi.com/2227-9059/11/9/2394Alzheimer’slumbar spinal fluidplasmacytokinescognitive dysfunctioninflammation |
| spellingShingle | Suzanne M. de la Monte Ming Tong Andrew J. Hapel Concordant and Discordant Cerebrospinal Fluid and Plasma Cytokine and Chemokine Responses in Mild Cognitive Impairment and Early-Stage Alzheimer’s Disease Biomedicines Alzheimer’s lumbar spinal fluid plasma cytokines cognitive dysfunction inflammation |
| title | Concordant and Discordant Cerebrospinal Fluid and Plasma Cytokine and Chemokine Responses in Mild Cognitive Impairment and Early-Stage Alzheimer’s Disease |
| title_full | Concordant and Discordant Cerebrospinal Fluid and Plasma Cytokine and Chemokine Responses in Mild Cognitive Impairment and Early-Stage Alzheimer’s Disease |
| title_fullStr | Concordant and Discordant Cerebrospinal Fluid and Plasma Cytokine and Chemokine Responses in Mild Cognitive Impairment and Early-Stage Alzheimer’s Disease |
| title_full_unstemmed | Concordant and Discordant Cerebrospinal Fluid and Plasma Cytokine and Chemokine Responses in Mild Cognitive Impairment and Early-Stage Alzheimer’s Disease |
| title_short | Concordant and Discordant Cerebrospinal Fluid and Plasma Cytokine and Chemokine Responses in Mild Cognitive Impairment and Early-Stage Alzheimer’s Disease |
| title_sort | concordant and discordant cerebrospinal fluid and plasma cytokine and chemokine responses in mild cognitive impairment and early stage alzheimer s disease |
| topic | Alzheimer’s lumbar spinal fluid plasma cytokines cognitive dysfunction inflammation |
| url | https://www.mdpi.com/2227-9059/11/9/2394 |
| work_keys_str_mv | AT suzannemdelamonte concordantanddiscordantcerebrospinalfluidandplasmacytokineandchemokineresponsesinmildcognitiveimpairmentandearlystagealzheimersdisease AT mingtong concordantanddiscordantcerebrospinalfluidandplasmacytokineandchemokineresponsesinmildcognitiveimpairmentandearlystagealzheimersdisease AT andrewjhapel concordantanddiscordantcerebrospinalfluidandplasmacytokineandchemokineresponsesinmildcognitiveimpairmentandearlystagealzheimersdisease |