Blood-based therapies to combat neurodegenerative diseases.

Neurodegeneration, known as the progressive loss of neurons in terms of their structure and function, is the principal pathophysiological change found in the majority of brain-related disorders. Ageing has been considered the most well-established risk factor in most common neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). There is currently no effective treatment or cure for these diseases; the approved therapeutic options to date are only for palliative care. Ageing and neurodegenerative diseases are closely intertwined; reversing the aspects of brain ageing could theoretically mitigate age-related neurodegeneration. Ever since the regenerative properties of young blood on aged tissues came to light, substantial efforts have been focused on identifying and characterizing the circulating factors in the young and old systemic milieu that may attenuate or accentuate brain ageing and neurodegeneration. Later studies discovered the superiority of old plasma dilution in tissue rejuvenation, which is achieved through a molecular reset of the systemic proteome. These findings supported the use of therapeutic blood exchange for the treatment of degenerative diseases in older individuals. The first objective of this article is to explore the rejuvenating properties of blood-based therapies in the ageing brains and their therapeutic effects on AD. Then, we also look into the clinical applications, various limitations, and challenges associated with blood-based therapies for AD patients.

Neural correlates of beneficial effects of young plasma treatment in aged mice: PET-SPM analyses and neuro-behavioural/molecular biological studies.

PURPOSE: To investigate the in vivo neurofunctional changes and therapeutic effects of young blood plasma (YBP) in aged mice, as well as the molecular mechanisms underlying the therapeutic effects of YBP ex vivo and in vitro. METHODS: Aged C57/BL6 mice received systemic administrations of phosphate-buffered saline (PBS) or YBP twice a week, for 4 weeks. In vivo 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) under conscious state and cognitive behavioural tests were performed after 4-week treatment. In addition, an in vitro senescent model was established, and the expressions of key cognition-associated proteins and/or the alterations of key neuronal pathways were analysed in both brain tissues and cultured cells. RESULTS: Aged mice treated with YBP demonstrated higher glucose metabolism in the right hippocampus and bilateral somatosensory cortices, and lower glucose metabolism in the right bed nucleus of stria terminalis and left cerebellum. YBP treatment exerted beneficial effects on the spatial and long-term social recognition memory, and significantly increased the expressions of several cognition-related proteins and altered the key neuronal signalling pathways in the hippocampus and somatosensory cortex. Further in vitro studies suggested that YBP but not aged blood plasma significantly upregulated the expressions of several cognition-associated proteins. CONCLUSION: Our results highlight the role of the hippocampus and somatosensory cortex in YBP-induced beneficial effects on recognition memory in aged mice. 18F-FDG PET imaging under conscious state provides a new avenue for exploring the mechanisms underlying YBP treatment against age-related cognitive decline.

The effect of young blood plasma administration on gut microbiota in middle-aged rats.

Numerous in-depth studies continue to reveal the many benefits of gut microbiota and young blood plasma administration. Dysbiosis, which occurs in the intestinal microbiota, especially in the aging process, is associated with many metabolic and cognitive disorders. Therefore, many studies aim to reverse the dysbiosis that occurs. There are also studies showing that young blood plasma application reverses the effects of aging at the level of many tissues and organs. Today, while research continues to reveal all the benefits of young blood plasma application in terms of health, blood plasma centers are also being established. In this study, we aimed to reveal the impact of young blood plasma, administered for 1 month, on the intestinal microbiota of middle-aged rats. After detailed metagenome analysis, alpha diversity indices demonstrated greater bacterial richness in the microbiota of plasma-administered rats compared with control rats. In addition, the Firmicutes/Bacteroidetes ratio was significantly diminished in plasma group microbiota, confirming possible rejuvenation properties of young plasma. Furthermore, increased counts of Bifidobacterium longum, Coprococcus catus, and Romboutsia ilealis species were measured in plasma-administered rats. The study revealed many fluctuations in different bacterial taxonomic units of the microbiota that could be valuable in future research on blood-based anti-aging treatments.

Young blood plasma reduces Alzheimer's disease-like brain pathologies and ameliorates cognitive impairment in 3×Tg-AD mice.

BACKGROUND: Recent studies indicated that circulatory factors in blood plasma from young animals can reactivate neurogenesis, restore synaptic plasticity, and improve cognitive function in aged animals. Here, we investigated if young plasma could have a possible therapeutic effect for treatment of Alzheimer's disease (AD)-like pathologies and cognitive impairment in triple-transgenic AD (3×Tg-AD) mice. METHODS: We intravenously injected plasma from 2- to 3-month-old C57BL/6 J wild-type mice into 16-17-month-old 3×Tg-AD mice twice a week for 8 weeks. The behavioral tests including open field, novel object recognition, Morris water maze, and reversal Morris water maze were conducted after 4-week plasma injections. The effect of young plasma on tau and Aß pathologies and on the levels of synaptic proteins and neuroinflammation were assessed by Western blots and immunohistochemical staining. RESULTS: Young plasma treatment improved short-term memory in the novel object recognition test and enhanced the spatial learning and memory in Morris water maze test and reversal Morris water maze test. Biochemical studies revealed that young plasma treatment reduced both tau and Aß pathologies, as well as neuroinflammation in the mouse brain. However, we did not detect any significant changes in levels of synaptic proteins or the dentate gyrus neurogenesis in the mouse brain after the treatment with young plasma. CONCLUSIONS: These data indicate that young blood plasma not only ameliorates tau and Aß pathologies but also enhances the cognitive function in 3×Tg-AD mice. These findings suggest that transfusion with young blood plasma could be a potentially effective treatment for AD.