Alterations in Immune Responses Are Associated with Dysfunctional Intracellular Signaling in Peripheral Blood Mononuclear Cells of Men and Women with Mild Cognitive Impairment and Alzheimer’s disease
Deficits in the neuroendocrine-immune network in the periphery associated with the onset and progression of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) have not been extensively studied. The present study correlatively examines the association between cell-mediated immune responses,...
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| Veröffentlicht in: | Molecular neurobiology 2024-05, Vol.61 (5), p.2964-2977 |
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| creator | Vasantharekha, Ramasamy Priyanka, Hannah P. Nair, Rahul S. Hima, Lalgi Pratap, Uday P. Srinivasan, Avathvadi V. ThyagaRajan, Srinivasan |
| description | Deficits in the neuroendocrine-immune network in the periphery associated with the onset and progression of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) have not been extensively studied. The present study correlatively examines the association between cell-mediated immune responses, stress hormones, amyloid precursor protein (APP) expression, peripheral blood mononuclear cells (PBMC), and intracellular signaling molecules in the pathophysiology of MCI and AD compared to adults. Serum APP, lymphocyte proliferation, total cholinesterase (TChE), butyrylcholinesterase (BChE) activities, cytokines (IL-2, IFN-γ, IL-6, and TNF-α), and intracellular signaling molecules (p-ERK, p-CREB, and p-Akt) were measured in the PBMCs of adult, old, MCI, and AD men and women initially and after 3 years in the same population. An age- and disease-associated decline in mini-mental state examination (MMSE) scores and lymphocyte proliferation of MCI and AD men and women were observed. An age- and disease-related increase in serum APP, cortisol levels, and TChE activity were observed in men and women. Enhanced production of Th1 cytokine, IL-2, pro-inflammatory cytokines, and suppressed intracellular transcription factors may promote the inflammatory environment in MCI and AD patients. The expression of CREB and Akt was lower in MCI and AD men, while the expression of p-ERK was higher, and p-CREB was lower in MCI and AD women after 3 years. These results suggest that changes in specific intracellular signaling pathways may influence alterations in cell-mediated immunity to promote disease progression in MCI and AD patients. |
| doi_str_mv | 10.1007/s12035-023-03764-3 |
| format | Article |
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The present study correlatively examines the association between cell-mediated immune responses, stress hormones, amyloid precursor protein (APP) expression, peripheral blood mononuclear cells (PBMC), and intracellular signaling molecules in the pathophysiology of MCI and AD compared to adults. Serum APP, lymphocyte proliferation, total cholinesterase (TChE), butyrylcholinesterase (BChE) activities, cytokines (IL-2, IFN-γ, IL-6, and TNF-α), and intracellular signaling molecules (p-ERK, p-CREB, and p-Akt) were measured in the PBMCs of adult, old, MCI, and AD men and women initially and after 3 years in the same population. An age- and disease-associated decline in mini-mental state examination (MMSE) scores and lymphocyte proliferation of MCI and AD men and women were observed. An age- and disease-related increase in serum APP, cortisol levels, and TChE activity were observed in men and women. Enhanced production of Th1 cytokine, IL-2, pro-inflammatory cytokines, and suppressed intracellular transcription factors may promote the inflammatory environment in MCI and AD patients. The expression of CREB and Akt was lower in MCI and AD men, while the expression of p-ERK was higher, and p-CREB was lower in MCI and AD women after 3 years. These results suggest that changes in specific intracellular signaling pathways may influence alterations in cell-mediated immunity to promote disease progression in MCI and AD patients.</description><subject>Age</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>AKT protein</subject><subject>Alzheimer Disease - blood</subject><subject>Alzheimer Disease - immunology</subject><subject>Alzheimer's disease</subject><subject>Amyloid beta-Protein Precursor - metabolism</subject><subject>Amyloid precursor protein</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Cell Proliferation</subject><subject>Cell-mediated immunity</subject><subject>Cognitive ability</subject><subject>Cognitive Dysfunction - blood</subject><subject>Cognitive Dysfunction - immunology</subject><subject>Cyclic AMP response element-binding protein</subject><subject>Cytokines</subject><subject>Cytokines - blood</subject><subject>Cytokines - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Immune response (cell-mediated)</subject><subject>Inflammation</subject><subject>Interleukin 2</subject><subject>Intracellular</subject><subject>Intracellular signalling</subject><subject>Intracellular Space - metabolism</subject><subject>Leukocytes (mononuclear)</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neurobiology</subject><subject>Neurodegenerative diseases</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Peripheral blood mononuclear cells</subject><subject>Signal Transduction</subject><subject>Transcription factors</subject><subject>Tumor necrosis factor-α</subject><subject>Women</subject><subject>γ-Interferon</subject><issn>0893-7648</issn><issn>1559-1182</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUuOEzEQhlsIxISBC7BAltiwafCj3baXTXhFmgjEQywtp12deOS2g90NGlZcgyNxDU6CkwwgsWBlq-r7_yr7r6r7BD8mGIsnmVDMeI0pqzETbVOzG9WCcK5qQiS9WS2wVKwuDXlW3cn5EmNKCRa3qzMmFBcNZYvqR-cnSGZyMWTkAlqN4xwAvYW8LxXIqEuAupxj78wEFn1x0w49u8rDHPqDyHi0ClMyPXg_e5PQO7ctRRe2B7c3kNx-V_w9eupjtGgdQwxz76GQyyLJKA5oDQGZYNHHOJbbccLaeYuWcRvc5D5D2WpvXCrd6Qh2_usO3Ajp57fvGVmXwWS4W90ajM9w7_o8rz68eP5--aq-eP1ytewu6p7RdqqVGZQR2PKWcaOINXbYtERyY5lUhhsuhei5YBveSGoH2qgWWwZ2M7QCetOw8-rRyXef4qcZ8qRHlw_PNwHinDWVUiklSEsK-vAf9DLOqXxP1gw3bSsEkbJQ9ET1KeacYND75EaTrjTB-hC0PgWtS9D6GLRmRfTg2nrejGD_SH4nWwB2AnJphS2kv7P_Y_sLnKm4ng</recordid><startdate>20240501</startdate><enddate>20240501</enddate><creator>Vasantharekha, Ramasamy</creator><creator>Priyanka, Hannah P.</creator><creator>Nair, Rahul S.</creator><creator>Hima, Lalgi</creator><creator>Pratap, Uday P.</creator><creator>Srinivasan, Avathvadi V.</creator><creator>ThyagaRajan, Srinivasan</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7730-0728</orcidid></search><sort><creationdate>20240501</creationdate><title>Alterations in Immune Responses Are Associated with Dysfunctional Intracellular Signaling in Peripheral Blood Mononuclear Cells of Men and Women with Mild Cognitive Impairment and Alzheimer’s disease</title><author>Vasantharekha, Ramasamy ; 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The present study correlatively examines the association between cell-mediated immune responses, stress hormones, amyloid precursor protein (APP) expression, peripheral blood mononuclear cells (PBMC), and intracellular signaling molecules in the pathophysiology of MCI and AD compared to adults. Serum APP, lymphocyte proliferation, total cholinesterase (TChE), butyrylcholinesterase (BChE) activities, cytokines (IL-2, IFN-γ, IL-6, and TNF-α), and intracellular signaling molecules (p-ERK, p-CREB, and p-Akt) were measured in the PBMCs of adult, old, MCI, and AD men and women initially and after 3 years in the same population. An age- and disease-associated decline in mini-mental state examination (MMSE) scores and lymphocyte proliferation of MCI and AD men and women were observed. An age- and disease-related increase in serum APP, cortisol levels, and TChE activity were observed in men and women. Enhanced production of Th1 cytokine, IL-2, pro-inflammatory cytokines, and suppressed intracellular transcription factors may promote the inflammatory environment in MCI and AD patients. The expression of CREB and Akt was lower in MCI and AD men, while the expression of p-ERK was higher, and p-CREB was lower in MCI and AD women after 3 years. These results suggest that changes in specific intracellular signaling pathways may influence alterations in cell-mediated immunity to promote disease progression in MCI and AD patients.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>37957423</pmid><doi>10.1007/s12035-023-03764-3</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-7730-0728</orcidid></addata></record> |
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| subjects | Age Aged Aged, 80 and over AKT protein Alzheimer Disease - blood Alzheimer Disease - immunology Alzheimer's disease Amyloid beta-Protein Precursor - metabolism Amyloid precursor protein Biomedical and Life Sciences Biomedicine Cell Biology Cell Proliferation Cell-mediated immunity Cognitive ability Cognitive Dysfunction - blood Cognitive Dysfunction - immunology Cyclic AMP response element-binding protein Cytokines Cytokines - blood Cytokines - metabolism Female Humans Immune response (cell-mediated) Inflammation Interleukin 2 Intracellular Intracellular signalling Intracellular Space - metabolism Leukocytes (mononuclear) Leukocytes, Mononuclear - metabolism Lymphocytes T Male Middle Aged Neurobiology Neurodegenerative diseases Neurology Neurosciences Peripheral blood mononuclear cells Signal Transduction Transcription factors Tumor necrosis factor-α Women γ-Interferon |
| title | Alterations in Immune Responses Are Associated with Dysfunctional Intracellular Signaling in Peripheral Blood Mononuclear Cells of Men and Women with Mild Cognitive Impairment and Alzheimer’s disease |
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