Abstract
Alzheimer's disease patients display neuropathological lesions, including the accumulation of amyloid-beta (Aβ) peptide and neurofibrillary tangles. Although the mechanisms causing the neurodegenerative process are largely unknown, increasing evidence highlights a critical role of immunity in the pathogenesis of Alzheimer's disease. In the present study, we investigated the role of regulatory T cells (Tregs) on Alzheimer's disease progression. First, we explored the effect of Tregs (CD4+CD25+ T cells) and Teffs (CD4+CD25− T cells) in an adoptive transfer model. Systemic transplantation of purified Tregs into 3xTg-AD mice improved cognitive function and reduced deposition of Aβ plaques. In contrast, adoptive transfer of Teffs diminished behavioral function and cytokine production. Next, we transiently depleted Treg population using an anti-CD25 antibody (PC61). Depletion of Tregs for four months resulted in a marked aggravation of the spatial learning deficits of six-month-old 3xTg-AD mice. Additionally, it resulted in decreasing glucose metabolism, as assessed by positron emission tomography (PET) with 18F-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) neuroimaging. Importantly, the deposition of Aβ plaques and microglia/macrophage was increased in the hippocampal CA1 and CA3 regions of the Treg depleted 3xTg-AD compared to the vehicle-treated 3xTg-AD group. Our finding suggested that systemic Treg administration ameliorates disease progression and could be an effective Alzheimer's disease treatment.
Highlights
Alzheimer’s disease (AD) is the most prevalent form of dementia in the elderly individuals, characterized by the progressive deterioration of cognitive ability, accumulation of amyloid-β peptide and synaptic alterations [1]
We transplanted Treg cells into 3xTg-AD transgenic mice to ameliorate Alzheimer-like pathology
Our results showed that Treg cells improved spatial learning and memory of 3xTg-AD mice and contributed to the reduced cerebral Aβ burden and decreased inflammatory cytokine productions
Summary
Alzheimer’s disease (AD) is the most prevalent form of dementia in the elderly individuals, characterized by the progressive deterioration of cognitive ability, accumulation of amyloid-β peptide and synaptic alterations [1]. The neuropathological findings of AD are the extracellular deposition of amyloid beta peptide in the form of senile plaques and the formation of intracellular neurofibrillary tangles consist of hyperphosphorylated tau protein [3, 4]. Clinical studies of Aβ-directed vaccination strategies have revealed that treatment after disease onset has little effect on the cognition of patients and has serious adverse effects [9, 10]. Despite the extensive research effort to find effective treatment for Alzheimer’s patients, current therapies are no significant benefits
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