Circulating miRNAs as potential biomarkers in alzheimer's disease

Daniela Galimberti, Chiara Villa, Chiara Fenoglio, Maria Serpente, Laura Ghezzi, Sara M G Cioffi, Andrea Arighi, Giorgio Fumagalli, Elio Scarpini

Research output: Contribution to journalArticle

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Abstract

Several micro(mi)RNA are deregulated in brain, cerebrospinal fluid (CSF), and serum/plasma from patients with Alzheimer's disease (AD). The aim of the study was to profile circulating miRNAs in serum as non-invasive biomarkers for AD, correlating them with those identified in CSF, the biological fluid which better reflects biochemical changes occurring during pathological processes in the brain and may provide a robust indicator of AD-related disease pathogenesis thanks to the evidence of low amyloid and high levels of tau and hyperphosphorylated tau. Using a two-step analysis (array and validation through real-time PCR), a down-regulation (mean fold change ± SEM) of miR-125b (0.415 ± 0.11 versus 1.381 ± 0.36, p = 0.009), miR-23a (0.111 ± 0.03 versus 0.732 ± 0.14, p <0.001), and miR-26b (0.414 ± 0.11 versus 1.353 ± 0.39, p <0.01), out of 84 tested, was shown in serum from 22 AD patients compared with 18 non-inflammatory and 8 inflammatory neurological controls (NINDCs and INDCs) and 10 patients with frontotemporal dementia. Significant down-regulation of miR-125b and miR-26b was also confirmed in CSF from AD patients versus NINDCs (miR-125b: 0.089 ± 0.03 versus 0.230 ± 0.08, p <0.001; miR-26b: 0.217 ± 0.06 versus 1.255 ± 0.29, p <0.001, mean fold change ± SEM, respectively), whereas data were not replicated for miR-23a. In serum, miR-125b had an AUC of 0.82 to distinguish AD from NINDCs (95% CI: 0.65-0.98, p = 0.005). In conclusion, we demonstrated that cell-free miR-125b serum levels are decreased in serum from patients with AD as compared with NINDC and distinguish between AD and NINDCs with an accuracy of 82%. Supplementary Figure 1. A) Array miRNA list; B) Heat map. Data are expressed as fold change (fold difference) in Alzheimer's disease patients versus controls and normalized on cel-miR-39. Each square represents a single miRNA. Green indicates down-regulation and red indicates upregulation.

Original languageEnglish
Pages (from-to)1261-1267
Number of pages7
JournalJournal of Alzheimer's Disease
Volume42
Issue number4
DOIs
Publication statusPublished - 2014

Fingerprint

MicroRNAs
Alzheimer Disease
Biomarkers
Serum
Cerebrospinal Fluid
Down-Regulation
Frontotemporal Dementia
Brain
Pathologic Processes
Amyloid
Area Under Curve
Real-Time Polymerase Chain Reaction
Up-Regulation
Hot Temperature

Keywords

  • Alzheimer's disease
  • biomarker
  • miRNA
  • serum

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology
  • Medicine(all)

Cite this

Circulating miRNAs as potential biomarkers in alzheimer's disease. / Galimberti, Daniela; Villa, Chiara; Fenoglio, Chiara; Serpente, Maria; Ghezzi, Laura; Cioffi, Sara M G; Arighi, Andrea; Fumagalli, Giorgio; Scarpini, Elio.

In: Journal of Alzheimer's Disease, Vol. 42, No. 4, 2014, p. 1261-1267.

Research output: Contribution to journalArticle

Galimberti, Daniela ; Villa, Chiara ; Fenoglio, Chiara ; Serpente, Maria ; Ghezzi, Laura ; Cioffi, Sara M G ; Arighi, Andrea ; Fumagalli, Giorgio ; Scarpini, Elio. / Circulating miRNAs as potential biomarkers in alzheimer's disease. In: Journal of Alzheimer's Disease. 2014 ; Vol. 42, No. 4. pp. 1261-1267.
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