Intravenous administration of mesenchymal stem cells reduces Tau phosphorylation and inflammation in the 3xTg-AD mouse model of Alzheimer's disease

Amanda Ferreira Neves, Christian Camargo, Courtney Premer, Joshua M. Hare, Bernard S. Baumel, Milena Pinto

Research output: Contribution to journalArticlepeer-review

Abstract

Mesenchymal stem cell (MSC) administration is a novel and promising therapeutic approach for Alzheimer's disease (AD). Focusing on an intervention easily translatable into clinical practice, we administered allogeneic bone marrow-derived MSCs intravenously in a mouse model of AD (3xTg-AD). We systematically evaluated the effects of a single-dose and multiple-doses of MSCs in young and old mice (5 or 10 months old), comparing the short-term and long-term effects after 1, 2, or 7 months of treatment. A single dose of MSCs in young mice attenuated neuroinflammation 1 and 7 months after injection, whereas multiple-doses did not show any effect. Multiple-doses of MSCs (administered at 5 to 12 mo, or 10 to 12 mo) reduced the β-secretase cleavage of the amyloid precursor protein, although levels of Aβ-42 did not change. Most interestingly, multiple doses of MSCs affected tau hyperphosphorylation. MSCs administered in young mice for 7 months decreased the pathological tau phosphorylation at T205, S214, and T231. MSCs administered in old mice for 2 months decreased tau phosphorylation at S396. Our findings show how different timing and frequency of MSC injections can affect and modulate several aspects of the AD-like neuropathology in the 3xTg-AD mouse model, strengthening the concept of fine-tuning MSC therapy for Alzheimer's disease.

Original languageEnglish (US)
Article number113706
JournalExperimental neurology
Volume341
DOIs
StatePublished - Jul 2021

Keywords

  • 3xTg-AD mice
  • Alzheimer's disease
  • Amyloid-β
  • Mesenchymal stem cells
  • Neuroinflammation
  • Tau phosphorylation

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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