IL-1β, IL-6, IL-10, and TNFα single nucleotide polymorphisms are associated with cerebrospinal fluid levels of biomarkers of Alzheimer’s disease

Abstract Background Neuroinflammation plays an important role in Alzheimer’s disease (AD). During this process, activated microglia release pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1β, IL-6 and tumor necrosis factor α (TNFα) that participate in neuron damage. However, anti-inflammatory cytokines (such as IL-10), which maintain homeostasis of immune response, are also released. Previous studies showed the association of IL-1α -889C/T (rs1800587), IL-1β -1473G/C (rs1143623), IL-6 -174C/G (rs1800795), IL-10 -1082G/A (rs1800896) and TNFα -308A/G (rs1800629) polymorphisms with AD.Methods In this study, we assessed whether people carrying certain genotypes in these polymorphisms are more prone to develop AD-related pathology, reflected by pathological levels of cerebrospinal fluid (CSF) AD biomarkers including amyloid β1–42 (Aβ1–42), total tau (t‐tau), tau phosphorylated at Thr 181 (p‐tau181), Ser 199 (p‐tau199), and Thr 231 (p‐tau231), and visinin‐like protein 1 (VILIP‐1). The study included 115 AD patients, 53 patients with mild cognitive impairment (MCI), 11 healthy controls, and 54 patients with other causes of dementia.Results A significant increase in p-tau CSF levels was found in patients with the AA IL-10 -1082G/A and GG TNFα -308A/G genotypes, and in carriers of a G allele in IL-1β -1473C/G and IL-6 -174C/G polymorphisms. T-tau levels were increased while Aβ1-42 levels were decreased in carriers of a G allele in IL-1β -1473C/G polymorphism. An increase in VILIP-1 levels was observed in patients with CG and GG IL-1β -1473C/G, GC IL-6 -174C/G and GG TNFα -308A/G genotype.Conclusions These results suggest that persons carrying certain genotypes in IL10 (-1082G/A), IL1β (1473C/G), IL6 (-174C/G) and TNFα (-308A/G) could be more vulnerable to development of neuroinglammation, and consequently of AD.

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Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease

Frontiers in Neurology ◽

10.3389/fneur.2021.543866 ◽

2021 ◽

Vol 12 ◽

Author(s):

Masaki Ikeda ◽

Sayaka Kodaira ◽

Hiroo Kasahara ◽

Eriko Takai ◽

Kazuaki Nagashima ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Cerebral Microbleeds ◽

The Other ◽

Cortical Atrophy ◽

Amyloid Angiopathy ◽

Temporal Area ◽

Csf Levels ◽

T Tau

Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aβ) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and late-onset amnestic dominant AD, logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) who were compatible with the AD criteria. We then examined the levels of cerebrospinal fluid (CSF) biomarkers [Aβ1-42, Aβ1-40, Aβ1-38, phosphorylated tau 181 (P-Tau), total tau (T-Tau), neurofilament light chain (NFL), and chitinase 3-like 1 protein (YKL-40)], analyzed the number and localization of CMBs, and measured the cerebral blood flow (CBF) volume by 99mTc-ethyl cysteinate dimer single photon emission computerized tomography (99mTc ECD-SPECT), as well as the mean cortical standard uptake value ratio by 11C-labeled Pittsburgh Compound B-positron emission tomography (11C PiB-PET). Lobar CMBs in lvPPA were distributed in the temporal, frontal, and parietal lobes with the left side predominance, while the CBF volume in lvPPA significantly decreased in the left temporal area, where the number of lobar CMBs and the CBF volumes showed a significant inversely correlation. The CSF levels of NFL in lvPPA were significantly higher compared to the other AD subtypes and non-demented subjects. The numbers of lobar CMBs significantly increased the CSF levels of NFL in the total AD patients, additionally, among AD subtypes, the CSF levels of NFL in lvPPA predominantly were higher by increasing number of lobar CMBs. On the other hand, the CSF levels of Aβ1-38, Aβ1-40, Aβ1-42, P-Tau, and T-Tau were lower by increasing number of lobar CMBs in the total AD patients. These findings may suggest that aberrant brain hypoperfusion in lvPPA was derived from the brain atrophy due to neurodegeneration, and possibly may involve the aberrant microcirculation causing by lobar CMBs and cerebrovascular injuries, with the left side dominance, consequently leading to a clinical phenotype of logopenic variant.

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Cognitive Dispersion Is Not Associated with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease: Results from the European Prevention of Alzheimer’s Dementia (EPAD) v500.0 Cohort

Journal of Alzheimer s Disease ◽

10.3233/jad-200514 ◽

2020 ◽

Vol 78 (1) ◽

pp. 185-194

Author(s):

Tam Watermeyer ◽

Alejandra Marroig ◽

Craig W. Ritchie ◽

Karen Ritchie ◽

Kaj Blennow ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Cognitive Aging ◽

Amyloid Β ◽

Cost Effective ◽

Csf Levels ◽

T Tau

Background: Cognitive dispersion, variation in performance across cognitive domains, is posited as a non-invasive and cost-effective marker of early neurodegeneration. Little work has explored associations between cognitive dispersion and Alzheimer’s disease (AD) biomarkers in healthy older adults. Even less is known about the influence or interaction of biomarkers reflecting brain pathophysiology or other risk factors on cognitive dispersion scores. Objective: The main aim of this study was to examine whether higher cognitive dispersion was associated with cerebrospinal fluid (CSF) levels of amyloid-β (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), and amyloid positivity in a cohort of older adults at various severities of AD. A secondary aim was to explore which AD risk factors were associated with cognitive dispersion scores. Methods: Linear and logistic regression analyses explored the associations between dispersion and CSF levels of Aβ42, t-tau, and p-tau and amyloid positivity (Aβ42 < 1000 pg/ml). Relationships between sociodemographics, APOE ɛ4 status, family history of dementia, and levels of depression and dispersion were also assessed. Results: Dispersion did not emerge as associated with any of the analytes nor amyloid positivity. Older (β= –0.007, SE = 0.002, p = 0.001) and less educated (β= –0.009, SE = 0.003, p = 0.009) individuals showed greater dispersion. Conclusion: Dispersion was not associated with AD pathology, but was associated with age and years of education, highlighting individual differences in cognitive aging. The use of this metric as a screening tool for existing AD pathology is not supported by our analyses. Follow-up work will determine if dispersion scores can predict changes in biomarker levels and/or positivity status longitudinally.

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Asymptomatic Carriers of Presenilin-1 E318G Variant Show no Cerebrospinal Fluid Biochemical Signs Suggestive of Alzheimer’s disease in a Family with Late-onset Dementia

Current Alzheimer Research ◽

10.2174/1567205015666181031150345 ◽

2018 ◽

Vol 16 (1) ◽

pp. 1-7

Author(s):

Vladimiro Artuso ◽

Luisa Benussi ◽

Roberta Ghidoni ◽

Soraya Moradi-Bachiller ◽

Federica Fusco ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Late Onset ◽

Presenilin 1 ◽

Amyloid Peptides ◽

Csf Levels ◽

T Tau ◽

Late Onset Dementia

Background: Presenilin-1 (PSEN-1) is a component of the γ-secretase complex involved in β-amyloid Precursor Protein (AβPP) processing. Usually, Alzheimer’s disease (AD)-linked mutations in the PSEN-1 gene lead to the early onset and increase the production of the aggregation-prone peptide Aβ42. However, the PSEN-1 E318G variant has an unclear pathogenic role and is recently reported as a genetic risk factor for AD. In particular, E318G variant presence correlated with increased cerebrospinal fluid (CSF) levels of Total Tau (t-tau) and Phosphorylated Tau (p-tau). Objective: We describe a large Italian family, which we followed from January 2003 to January 2018, with the late-onset AD and the E318G variant, with the aim of assessing E318G-associated CSF or plasma biochemical changes in biomarkers of dementia. Method: CSF Aβ42, t-tau and p-tau, plasma Aβ42 and Aβ40 were assessed by ELISA tests, while CSF amyloid peptides profile was investigated by mass spectrometry. Results: We did not find any changes in CSF biochemical markers (Aβ42, t-tau, p-tau and amyloid peptides) of asymptomatic E318G carriers in 2010 and 2012, but plasma Aβ40 was increased at the same times. From 2003 to 2018, no asymptomatic E318G carrier developed AD. Conclusion: Our follow-up of this family may help elucidate E318G’s role in AD and globally points to a null effect of this variant.

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Functional correlates of t-Tau, p-Tau and Aβ1–42 amyloid cerebrospinal fluid levels in Alzheimer’s disease

Nuclear Medicine Communications ◽

10.1097/mnm.0000000000000272 ◽

2015 ◽

Vol 36 (5) ◽

pp. 461-468 ◽

Cited By ~ 11

Author(s):

Agostino Chiaravalloti ◽

Alessandro Martorana ◽

Giacomo Koch ◽

Sofia Toniolo ◽

Daniele di Biagio ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Cerebrospinal Fluid Levels ◽

Fluid Levels ◽

T Tau

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Follow-up study on plasma and cerebrospinal fluid levels of B amyloids and tau proteins in patients with alzheimer's disease

European Psychiatry ◽

10.1016/s0924-9338(11)72213-1 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 506-506

Author(s):

Y. Fu ◽

S. Xiao

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Amyloid Β ◽

Tau Proteins ◽

Enzyme Linked Immunosorbent Assay ◽

Csf Levels ◽

Severity Of Dementia ◽

T Tau

AimsCompare baseline and 6-month follow-up plasma and cerebrospinal fluid (CSF) levels of amyloid β peptides 1–40 (Aβ1–40) and 1–42 (Aβ1–42), total tau protein (T-tau) and phosphorylated tau at threonine 231 (P-tau231) in patients with Alzheimer's disease (AD) and vascular dementia (VD).Methods21 patients with AD and 7 patients with VD based on the criteria of Diagnostic Statistical Manual 4th edition were assessed at baseline and 7 with AD and 6 with VD were re-assessed 6 months later. Assessments included the Mini-Mental State Exam (MMSE), the Global Deteriorate Scale (GDS), plasma and CSF levels of Aβ1–40 and Aβ1–42, and CSF levels of T-tau and P-tau231 (using a sandwich enzyme-linked immunosorbent assay).ResultsAt baseline there were significant differences between AD and VD patients in the mean CSF levels of T-tau (t=2.580, P=0.016), P-tau231 (t=4.014, P=0.000) and Aβ1–40 (t=2.766, P=0.010). At baseline in AD patients, duration of illness was negatively correlated with CSF P-tau231 levels (r=-0.485, P=0.026), MMSE scores (r=-0.565, P=0.008) and GDS scores (r=-0.482, P=0.027); and CSF Aβ1–42 levels were positively correlated to MMSE scores (r=0.565, P=0.008) and negatively correlated with GDS scores (r=-0.634, P=0.002). In the AD patients plasma Aβ1–40 levels increased significantly over the 6-month follow-up period (t=-2.735, P=0.041).ConclusionsPlasma Aβ1–40 levels increased significantly in AD patients after 6-months of follow-up, that means levels of plasma Aβ1–40 could imply the development of Alzheimer disease. Moreover, CSF P-tau231 and CSF Aβ1–42 levels are associated with the severity of dementia and cognitive impairment.

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Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Alzheimer's disease

Journal of Neural Transmission ◽

10.1007/bf01291887 ◽

1997 ◽

Vol 104 (6-7) ◽

pp. 703-710 ◽

Cited By ~ 66

Author(s):

F. J. Jiménez-Jiménez ◽

F. de Bustos ◽

J. A. Molina ◽

J. Benito-León ◽

A. Tallón-Barranco ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Vitamin E ◽

Alpha Tocopherol ◽

Cerebrospinal Fluid Levels ◽

Fluid Levels

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Evidence for an effect of single nucleotide polymorphisms in SORL1 on cerebrospinal fluid markers of Alzheimer’s disease

Future Neurology ◽

10.2217/fnl.12.10 ◽

2012 ◽

Vol 7 (2) ◽

pp. 123-126

Author(s):

Christiane Reitz

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Single Nucleotide Polymorphisms ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

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Cerebrospinal Fluid Levels of sAPPαand sAPPβin Lewy Body and Alzheimer's Disease: Clinical and Neurochemical Correlates

International Journal of Alzheimer s Disease ◽

10.4061/2011/495025 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Ezra Mulugeta ◽

Elisabet Londos ◽

Oskar Hansson ◽

Clive Ballard ◽

Ragnhild Skogseth ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Lewy Body ◽

Group Analysis ◽

Lewy Body Dementia ◽

Csf Biomarkers ◽

Commercial Kits ◽

Neurochemical Correlates ◽

Fluid Levels

We measured cerebrospinal fluid (CSF) levels of the soluble isoforms of amyloid precursor protein (APP; sAPPαsAPPβ) and other CSF biomarkers in 107 patients with Alzheimer's disease (AD), dementia with Lewy body dementia (DLB), Parkinson's disease dementia (PDD), and normal controls (NC) using commercial kits. DLB and PDD were combined in a Lewy body dementia group (LBD). No differences were observed in sAPPαand sAPPβlevels between the groups. Significant correlations were observed between sAPPαand sAPPβand between sAPPβand Mini-Mental State Examination scores in the total group analysis as well as when LBD and AD groups were analyzed separately. sAPPαand sAPPβlevels correlated with Aβ38, Aβ40, Aβ42, and Tau in the LBD group. In AD, sAPPαcorrelated with p-Tau and sAPPβwith Aβ40. The differential association between sAPPαand sAPPβwith Aβand Tau species between LBD and AD groups suggests a possible relationship with the underlying pathologies in LBD and AD.

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