Antibodies to Signaling Molecules and Receptors in Alzheimer's Disease are Associated with Psychomotor Slowing, Depression, and Poor Visuospatial Function

Lasse M Giil; Christian A Vedeler; Einar K Kristoffersen; Jan Erik Nordrehaug; Harald Heidecke; Ralf Dechend; Kai Schulze-Forster; Dominik N Muller; Victoria S von Goetze; Otavio Cabral-Marques; Gabriela Riemekasten; Petra Vogelsang; Staale Nygaard; Anders Lund; Dag Aarsland

doi:10.3233/JAD-170245

Antibodies to Signaling Molecules and Receptors in Alzheimer's Disease are Associated with Psychomotor Slowing, Depression, and Poor Visuospatial Function

Lasse M Giil, Christian A Vedeler, Einar K Kristoffersen, Jan Erik Nordrehaug, Harald Heidecke, Ralf Dechend, Kai Schulze-Forster, Dominik N Muller, Victoria S von Goetze, Otavio Cabral-Marques, Gabriela Riemekasten, Petra Vogelsang, Staale Nygaard, Anders Lund, Dag Aarsland

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

BACKGROUND: Alzheimer's disease (AD) is associated with several antibodies as well as signaling molecules and receptors. These may be detrimental in the presence of a disrupted blood-brain barrier (BBB).

OBJECTIVE: To investigate whether the levels of antibodies toward 33 signaling molecules involved in neurotransmitter, vascular, and immune functions were associated with AD and, within the AD group; cognitive function and mood.

METHODS: Antibodies in sera from patients with mild AD [(n = 91) defined as a Mini-Mental State Examination ≥ 20 or a Clinical Dementia Rating Scale≤1] and healthy controls (n = 102) were measured with enzyme-linked immunosorbent assays. Levels in AD and controls were compared by Mann-Whitney test. In the AD group, associations between antibodies and psychometric test scores were analyzed by robust regression. The false discovery threshold was set to 0.05.

RESULTS: Antibodies to serotonin receptors [5-HT2AR (effect size (r) = 0.21, p = 0.004), 5-HT2CR (r = 0.25, p = 0.0005) and 5-HT7R (r = 0.21, p = 0.003)], vascular endothelial growth factor receptor 1 [VEGFR1 (r = 0.29, p < 0.001)] and immune-receptors (Stabilin-1 (r = 0.23, p = 0.001) and C5aR1 (r = 0.21, p = 0.004) were higher in AD. Psychomotor speed was associated with D1R-abs (β 0.49, p < 0.001), depression with ETAR-abs (β 0.31, p < 0.001), and visuospatial function with 5-HT1AR-abs (β 0.27, p = 0.004) despite similar antibody levels compared to controls.

CONCLUSIONS: Antibody levels to VEGFR1, serotonergic receptors, and receptors in the immune system were increased in AD. Antibodies at similar levels as in controls were associated cognitive dysfunction and depression in AD.

Original language	English
Pages (from-to)	929-939
Number of pages	11
Journal	JOURNAL OF ALZHEIMERS DISEASE
Volume	59
Issue number	3
Early online date	1 Jul 2017
DOIs	https://doi.org/10.3233/JAD-170245
Publication status	Published - 29 Jul 2017

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3233/JAD-170245

Cite this

Giil, L. M., Vedeler, C. A., Kristoffersen, E. K., Nordrehaug, J. E., Heidecke, H., Dechend, R., Schulze-Forster, K., Muller, D. N., von Goetze, V. S., Cabral-Marques, O., Riemekasten, G., Vogelsang, P., Nygaard, S., Lund, A., & Aarsland, D. (2017). Antibodies to Signaling Molecules and Receptors in Alzheimer's Disease are Associated with Psychomotor Slowing, Depression, and Poor Visuospatial Function. JOURNAL OF ALZHEIMERS DISEASE, 59(3), 929-939. https://doi.org/10.3233/JAD-170245

@article{afd82e115b1c437daeb98f5ddd8e8947,

title = "Antibodies to Signaling Molecules and Receptors in Alzheimer's Disease are Associated with Psychomotor Slowing, Depression, and Poor Visuospatial Function",

abstract = "BACKGROUND: Alzheimer's disease (AD) is associated with several antibodies as well as signaling molecules and receptors. These may be detrimental in the presence of a disrupted blood-brain barrier (BBB).OBJECTIVE: To investigate whether the levels of antibodies toward 33 signaling molecules involved in neurotransmitter, vascular, and immune functions were associated with AD and, within the AD group; cognitive function and mood.METHODS: Antibodies in sera from patients with mild AD [(n = 91) defined as a Mini-Mental State Examination ≥ 20 or a Clinical Dementia Rating Scale≤1] and healthy controls (n = 102) were measured with enzyme-linked immunosorbent assays. Levels in AD and controls were compared by Mann-Whitney test. In the AD group, associations between antibodies and psychometric test scores were analyzed by robust regression. The false discovery threshold was set to 0.05.RESULTS: Antibodies to serotonin receptors [5-HT2AR (effect size (r) = 0.21, p = 0.004), 5-HT2CR (r = 0.25, p = 0.0005) and 5-HT7R (r = 0.21, p = 0.003)], vascular endothelial growth factor receptor 1 [VEGFR1 (r = 0.29, p < 0.001)] and immune-receptors (Stabilin-1 (r = 0.23, p = 0.001) and C5aR1 (r = 0.21, p = 0.004) were higher in AD. Psychomotor speed was associated with D1R-abs (β 0.49, p < 0.001), depression with ETAR-abs (β 0.31, p < 0.001), and visuospatial function with 5-HT1AR-abs (β 0.27, p = 0.004) despite similar antibody levels compared to controls.CONCLUSIONS: Antibody levels to VEGFR1, serotonergic receptors, and receptors in the immune system were increased in AD. Antibodies at similar levels as in controls were associated cognitive dysfunction and depression in AD.",

keywords = "Journal Article",

author = "Giil, {Lasse M} and Vedeler, {Christian A} and Kristoffersen, {Einar K} and Nordrehaug, {Jan Erik} and Harald Heidecke and Ralf Dechend and Kai Schulze-Forster and Muller, {Dominik N} and {von Goetze}, {Victoria S} and Otavio Cabral-Marques and Gabriela Riemekasten and Petra Vogelsang and Staale Nygaard and Anders Lund and Dag Aarsland",

year = "2017",

month = jul,

day = "29",

doi = "10.3233/JAD-170245",

language = "English",

volume = "59",

pages = "929--939",

journal = "JOURNAL OF ALZHEIMERS DISEASE",

issn = "1387-2877",

publisher = "IOS Press BV",

number = "3",

}

Giil, LM, Vedeler, CA, Kristoffersen, EK, Nordrehaug, JE, Heidecke, H, Dechend, R, Schulze-Forster, K, Muller, DN, von Goetze, VS, Cabral-Marques, O, Riemekasten, G, Vogelsang, P, Nygaard, S, Lund, A & Aarsland, D 2017, 'Antibodies to Signaling Molecules and Receptors in Alzheimer's Disease are Associated with Psychomotor Slowing, Depression, and Poor Visuospatial Function', JOURNAL OF ALZHEIMERS DISEASE, vol. 59, no. 3, pp. 929-939. https://doi.org/10.3233/JAD-170245

TY - JOUR

T1 - Antibodies to Signaling Molecules and Receptors in Alzheimer's Disease are Associated with Psychomotor Slowing, Depression, and Poor Visuospatial Function

AU - Giil, Lasse M

AU - Vedeler, Christian A

AU - Kristoffersen, Einar K

AU - Nordrehaug, Jan Erik

AU - Heidecke, Harald

AU - Dechend, Ralf

AU - Schulze-Forster, Kai

AU - Muller, Dominik N

AU - von Goetze, Victoria S

AU - Cabral-Marques, Otavio

AU - Riemekasten, Gabriela

AU - Vogelsang, Petra

AU - Nygaard, Staale

AU - Lund, Anders

AU - Aarsland, Dag

PY - 2017/7/29

Y1 - 2017/7/29

N2 - BACKGROUND: Alzheimer's disease (AD) is associated with several antibodies as well as signaling molecules and receptors. These may be detrimental in the presence of a disrupted blood-brain barrier (BBB).OBJECTIVE: To investigate whether the levels of antibodies toward 33 signaling molecules involved in neurotransmitter, vascular, and immune functions were associated with AD and, within the AD group; cognitive function and mood.METHODS: Antibodies in sera from patients with mild AD [(n = 91) defined as a Mini-Mental State Examination ≥ 20 or a Clinical Dementia Rating Scale≤1] and healthy controls (n = 102) were measured with enzyme-linked immunosorbent assays. Levels in AD and controls were compared by Mann-Whitney test. In the AD group, associations between antibodies and psychometric test scores were analyzed by robust regression. The false discovery threshold was set to 0.05.RESULTS: Antibodies to serotonin receptors [5-HT2AR (effect size (r) = 0.21, p = 0.004), 5-HT2CR (r = 0.25, p = 0.0005) and 5-HT7R (r = 0.21, p = 0.003)], vascular endothelial growth factor receptor 1 [VEGFR1 (r = 0.29, p < 0.001)] and immune-receptors (Stabilin-1 (r = 0.23, p = 0.001) and C5aR1 (r = 0.21, p = 0.004) were higher in AD. Psychomotor speed was associated with D1R-abs (β 0.49, p < 0.001), depression with ETAR-abs (β 0.31, p < 0.001), and visuospatial function with 5-HT1AR-abs (β 0.27, p = 0.004) despite similar antibody levels compared to controls.CONCLUSIONS: Antibody levels to VEGFR1, serotonergic receptors, and receptors in the immune system were increased in AD. Antibodies at similar levels as in controls were associated cognitive dysfunction and depression in AD.

AB - BACKGROUND: Alzheimer's disease (AD) is associated with several antibodies as well as signaling molecules and receptors. These may be detrimental in the presence of a disrupted blood-brain barrier (BBB).OBJECTIVE: To investigate whether the levels of antibodies toward 33 signaling molecules involved in neurotransmitter, vascular, and immune functions were associated with AD and, within the AD group; cognitive function and mood.METHODS: Antibodies in sera from patients with mild AD [(n = 91) defined as a Mini-Mental State Examination ≥ 20 or a Clinical Dementia Rating Scale≤1] and healthy controls (n = 102) were measured with enzyme-linked immunosorbent assays. Levels in AD and controls were compared by Mann-Whitney test. In the AD group, associations between antibodies and psychometric test scores were analyzed by robust regression. The false discovery threshold was set to 0.05.RESULTS: Antibodies to serotonin receptors [5-HT2AR (effect size (r) = 0.21, p = 0.004), 5-HT2CR (r = 0.25, p = 0.0005) and 5-HT7R (r = 0.21, p = 0.003)], vascular endothelial growth factor receptor 1 [VEGFR1 (r = 0.29, p < 0.001)] and immune-receptors (Stabilin-1 (r = 0.23, p = 0.001) and C5aR1 (r = 0.21, p = 0.004) were higher in AD. Psychomotor speed was associated with D1R-abs (β 0.49, p < 0.001), depression with ETAR-abs (β 0.31, p < 0.001), and visuospatial function with 5-HT1AR-abs (β 0.27, p = 0.004) despite similar antibody levels compared to controls.CONCLUSIONS: Antibody levels to VEGFR1, serotonergic receptors, and receptors in the immune system were increased in AD. Antibodies at similar levels as in controls were associated cognitive dysfunction and depression in AD.

KW - Journal Article

U2 - 10.3233/JAD-170245

DO - 10.3233/JAD-170245

M3 - Article

C2 - 28697567

SN - 1387-2877

VL - 59

SP - 929

EP - 939

JO - JOURNAL OF ALZHEIMERS DISEASE

JF - JOURNAL OF ALZHEIMERS DISEASE

IS - 3