Diabetes mellitus contributes to higher cerebrospinal fluid tau levels selectively in Alzheimer's disease patients with the APOE4 genotype
| Autor: | Nicola Biagio Mercuri, Alessandro Martorana, Chiara Giuseppina Bonomi, Caterina Motta, Martina Assogna, Vincenzo De Lucia, Roberta Semprini, Giacomo Koch, Alfredo Paolo Mascolo |
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| Rok vydání: | 2021 |
| Předmět: |
Apolipoprotein E
medicine.medical_specialty Genotype Tau protein Apolipoprotein E4 CSF tau Proteins Settore MED/26 Gastroenterology NO Cerebrospinal fluid Alzheimer Disease Diabetes mellitus Internal medicine medicine Diabetes Mellitus Humans Cognitive Dysfunction tau Alzheimer's disease tau diabetes CSF APOE Risk factor Pathological Amyloid beta-Peptides diabetes biology business.industry Neurodegeneration Alzheimer's disease medicine.disease Pathophysiology Peptide Fragments Neurology biology.protein Neurology (clinical) business APOE Biomarkers |
| Zdroj: | European journal of neurologyREFERENCES. 28(12) |
| ISSN: | 1468-1331 |
| Popis: | BACKGROUND AND PURPOSE Diabetes mellitus (DM) is considered a risk factor for Alzheimer's disease (AD) and shares some pathological pathways, such as activation of amyloid cascade and tau phosphorylation. The aim of the present study was to investigate to what extent DM could impact on neurodegeneration within the AD continuum, using β amyloid (A: Aβ1-42 ) and phosphorylated tau (T: p-tau) biomarkers to discriminate patients by Alzheimer's pathological change (A+/T-) and AD (A+/T+), according to the National Institute on Aging and Alzheimer's Association classification. In addition, we aimed to evaluate whether APOE genotype interacts with tau protein and glucose metabolism dysfunction to affect the pathological process. METHODS For this retrospective observational study, 1350 patients were recruited. The patients underwent a complete clinical investigation, neuropsychological assessment, lumbar puncture for cerebrospinal fluid (CSF) biomarkers analysis and APOE genotyping. RESULTS A total of 607 patients fulfilled the clinical criteria of mild cognitive impairment or early dementia. In A+T- patients (n = 350), DM did not influence CSF biomarker levels, while among A+T+ patients (n = 257) those with DM showed increased total tau (t-tau) levels compared to non-DM patients (DM: 919.4 ± 444 vs. non-DM: 773.1 ± 348.2; p = 0.04), but similar p-tau (p = 0.72) and Aβ1-42 levels (p = 0.83). Furthermore, multivariable regression analyses showed a significant association between DM and t-tau CSF levels, adjusting for age and sex, in APOE E4+ carriers (coefficient 222.83, 95% confidence interval 47.49-398.1; p = 0.01), but not in APOE E4- (p = 0.53). CONCLUSIONS The present study shows a clear dependency of CSF t-tau levels on DM for APOE E4+ AD patients, suggesting important differences between APOE E4-related and non-related disease, with key implications for AD pathophysiology and treatment. |
| Databáze: | OpenAIRE |
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