Vitamin B12 Levels in Alzheimer's Disease: Association with Clinical Features and Cytokine Production

Politis, Antonis; Olgiati, Paolo; Malitas, Petros; Albani, Diego; Signorini, A; Polito, Letizia; Mauro, Stefania De; Zisaki, Aikaterini; Piperi, Christina; Stamouli, Evangelia; Mailis, Antonis; Batelli, Sara; Forloni, Gianluigi; Ronchi, Diana De; Kalofoutis, Anastasios; Liappas, Ioannis; Serretti, Alessandro

doi:10.3233/jad-2010-1252

Cited by 40 publications

(27 citation statements)

References 59 publications

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“…This meta-analysis also revealed decreased levels of leptin and IL-1 receptor antagonist in AD patients and it is noteworthy that these authors concluded that IL-6 levels were inversely correlated with cognitive scores as ascertained by the MiniMental State Examination (MMSE) [70]. The last finding is unsurprising as there is a large body of evidence confirming that inflammatory signals can have a severe adverse effect on brain function, and is consistent with the work of several research teams which have reported that PIC levels in AD patients are positively associated with cognitive decline, increased frequency and severity of neuropsychiatric symptoms, disease severity and overall disease progression [71][72][73][74][75][76].…”

Section: Evidence Of Peripheral Inflammation In Adsupporting

confidence: 68%

Could Alzheimer’s Disease Originate in the Periphery and If So How So?

et al. 2018

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The classical amyloid cascade model for Alzheimer's disease (AD) has been challenged by several findings. Here, an alternative molecular neurobiological model is proposed. It is shown that the presence of the APOE ε4 allele, altered miRNA expression and epigenetic dysregulation in the promoter region and exon 1 of TREM2, as well as ANK1 hypermethylation and altered levels of histone post-translational methylation leading to increased transcription of TNFA, could variously explain increased levels of peripheral and central inflammation found in AD. In particular, as a result of increased activity of triggering receptor expressed on myeloid cells 2 (TREM-2), the presence of the apolipoprotein E4 (ApoE4) isoform, and changes in ANK1 expression, with subsequent changes in miR-486 leading to altered levels of protein kinase B (Akt), mechanistic (previously mammalian) target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3), all of which play major roles in microglial activation, proliferation and survival, there is activation of microglia, leading to the subsequent (further) production of cytokines, chemokines, nitric oxide, prostaglandins, reactive oxygen species, inducible nitric oxide synthase and cyclooxygenase-2, and other mediators of inflammation and neurotoxicity. These changes are associated with the development of amyloid and tau pathology, mitochondrial dysfunction (including impaired activity of the electron transport chain, depleted basal mitochondrial potential and oxidative damage to key tricarboxylic acid enzymes), synaptic dysfunction, altered glycogen synthase kinase-3 (GSK-3) activity, mTOR activation, impairment of autophagy, compromised ubiquitin-proteasome system, iron dyshomeostasis, changes in APP translation, amyloid plaque formation, tau hyperphosphorylation and neurofibrillary tangle formation.

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Section: Evidence Of Peripheral Inflammation In Adsupporting

confidence: 68%

Could Alzheimer’s Disease Originate in the Periphery and If So How So?

et al. 2018

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“…This sample was already reported [24][25][26]. Recruitment setting was the Neuropsychiatric Clinic of the Eginition Hospital in Athens, an academic center for neuropsychiatric disorders.…”

Section: Greek Samplementioning

confidence: 99%

Association of SORL1 Alleles with Late-Onset Alzheimer's Disease. Findings from the GIGAS_LOAD Study and Mega-Analysis

Olgiati

Politis²,

Albani

et al. 2012

CAR

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The pathophysiology of Alzheimer's disease (AD) is influenced by sorting-protein related receptor (sorLa) that is less expressed in AD patients. The gene encoding sorLa (SORL1) has been investigated as a susceptibility factor for late-onset AD (LOAD) with conflicting results. Our objectives were to confirm the association between SORL1 SNPs and LOAD in two independent South-European centers and to perform a mega-analysis of published samples. We analyzed three SORL1 SNPs (intron 6: rs668387; rs689021; rs641120) from the Greece-Italy Genetic Association Study on lateonset AD (GIGAS_LOAD). Greek sample included 96 patients with LOAD (DSM-IV) and 120 unrelated controls. In Italy, a community-based sample is ongoing. 47 LOAD patients and 165 controls were recruited until study endpoint. These samples and previously published ones (Alzgene) were pooled as in a single study. A test for trend was used to analyze genotype association. In the GIGAS_LOAD sample no association was detected between SORL1 genotypes and LOAD. Conversely all SNPs were associated with LOAD in mega-analysis based on ordinal classification of genotypes (Armitage's test: p < 0.001). Although our analysis of pooled samples has positive results for the association between SORL1 and AD, there is substantial heterogeneity across studies. Thus further examination into SORL1 SNPs and the population is necessary to determine the role of SORL1 in LOAD.

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“…A number of pro- and anti-inflammatory markers have been related to neuropsychiatric symptoms and functional level in aging and Alzheimer’s disease including TNFα [31], IL-1 [32, 33], IL-6 [30, 34, 35], IL-7 [36], IL-10 [37], IL-15 [38] and IL-18 [39]. …”

Section: Introductionmentioning

confidence: 99%

Biomarkers of Vascular Risk, Systemic Inflammation, and Microvascular Pathology and Neuropsychiatric Symptoms in Alzheimer's Disease

Hall

Wiechmann²,

Johnson³

et al. 2013

JAD

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Numerous serum and plasma based biomarkers of systemic inflammation have been linked to both neuropsychiatric disorders and Alzheimer’s disease. The present study investigated the relationship of clinical biomarkers of cardiovascular risk (cholesterol, triglycerides and homocysteine) and a panel of markers of systemic inflammation (CRP, TNF-α, IL1-ra, IL-7, IL-10, IL-15, IL18) and microvascular pathology (ICAM-1, VCAM-1) to neuropsychiatric symptoms in a sample with mild Alzheimer’s disease. Biomarker data was analyzed on a sample of 194 diagnosed with mild to moderate probable Alzheimer’s disease. The sample was composed of 127 females and 67 males. The presence of neuropsychiatric symptoms was gathered from interview with caretakers/family members using the Neuropsychiatric Inventory. For total sample IL15, VCAM (Vascular Adhesion Molecule) and triglycerides were significantly and negatively related to number of neuropsychiatric symptoms and total cholesterol and homocysteine were positively related and as a group accounted for 16.1% of the variance. When stratified by gender different patterns of significant biomarkers were found with relationships more robust for males for both total symptoms and symptom clusters. A combination of biomarkers of systemic inflammation, microvascular pathology and clinical biomarkers of cardiovascular risk can account for a significant portion of the variance in the occurrence of neuropsychiatric symptoms in Alzheimer’s disease supporting a vascular and inflammatory component of psychiatric disorders found in Alzheimer’s disease. Gender differences suggest distinct impact of specific risks with total cholesterol a measure of cardiovascular risk being the strongest marker for males and IL-15 a marker of inflammation being the strongest for females.

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Vitamin B12 Levels in Alzheimer's Disease: Association with Clinical Features and Cytokine Production

Cited by 40 publications

References 59 publications

Could Alzheimer’s Disease Originate in the Periphery and If So How So?

Could Alzheimer’s Disease Originate in the Periphery and If So How So?

Association of SORL1 Alleles with Late-Onset Alzheimer's Disease. Findings from the GIGAS_LOAD Study and Mega-Analysis

Biomarkers of Vascular Risk, Systemic Inflammation, and Microvascular Pathology and Neuropsychiatric Symptoms in Alzheimer's Disease

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