Aggregation of soluble, monomeric beta- amyloid (Abeta) to oligomeric and then insoluble fibrillar Abeta is a key pathogenic feature in development of Alzheimer's disease (AD). Increasing evidence suggests that toxicity is linked to diffusible Abeta oligomers, rather than to insoluble fibrils. The use of naturally occurring small molecules for inhibition of Abeta aggregation has recently attracted significant interest for development of effective therapeutic strategies against the disease. A natural polyphenolic flavone, Kaempferol-3-O-rhamnoside (K-3-rh), was utilized to investigate its effects on aggregation and cytotoxic effects of Abeta42 peptide. Several biochemical techniques were used to determine the conformational changes and cytotoxic effect of the peptide in the presence and absence of K-3-rh.

Alzheimer’s disease (AD) is the most common type of dementia in the elderly population. The disease is characterized by progressive memory loss, cerebral atrophy, extensive neuronal loss, synaptic alterations, brain inflammation, extracellular accumulation of amyloid-β (Aβ) plaques, and intracellular accumulation of hyper-phosphorylated tau (p-tau) protein. Many recent clinical trials have failed to show therapeutic benefit, likely because at the time in which patients exhibit clinical symptoms the brain is irreversibly damaged. In recent years, induced pluripotent stem cells (iPSCs) have been suggested as a promising cell therapy to recover brain functionality in neurodegenerative diseases such as AD. To evaluate the potential benefits of iPSCs on AD progression, we stereotaxically injected mouse iPSC-derived neural precursors (iPSC-NPCs) into the hippocampus of aged triple transgenic (3xTg-AD) mice harboring extensive pathological abnormalities typical of AD. Interestingly, iPSC-NPCs transplanted mice showed improved memory, synaptic plasticity, and reduced AD brain pathology, including a reduction of amyloid and tangles deposits. Our findings suggest that iPSC-NPCs might be a useful therapy that could produce benefit at the advanced clinical and pathological stages of AD.

Background: Neuroinflammation contributes to Parkinson's disease (PD) progression and motor dysfunction. Allogeneic human mesenchymal stem cells (allo‐hMSCs) may reduce neuroinflammation and improve motor symptoms. Objectives: To evaluate the efficacy of repeated intravenous doses of 10 × 10 ⁶ /kg allo‐hMSCs in improving motor symptoms in patients with PD (PwP). Methods: In this phase 2, randomized, placebo‐controlled trial (November 2020–July 2023), mild‐to‐moderate PwP received either three allo‐hMSC infusions, one placebo followed by two allo‐hMSC infusions, or three placebo infusions at 18‐week intervals. Follow‐up lasted 88 weeks. The primary outcome was a >70% posterior probability (PP) of a difference in the proportion of participants with ≥5‐point improvement in OFF‐medication Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale‐Part III (MDS‐UPDRS‐III) at week 62. Bayesian analysis was conducted using R v4.2.0. Results: Forty‐five PwP were enrolled. A larger proportion of subjects achieved a ≥5‐point improvement in MDS‐UPDRS‐III in the three‐infusion arm compared with placebo at week 62 (mean difference [MD]: 5.0%, PP = 93.7%), translating to a 16.9‐point improvement in MDS‐UPDRS‐III in the three‐infusion arm compared with a 14.6‐point improvement in the placebo arm. Conversely, fewer subjects in the two‐infusion arm compared with placebo showed ≥5‐point improvement at week 62 (MD: –62.4%, PP ≥ 99.9%), translating to only a 3.9‐point improvement in MDS‐UPDRS‐III in the two‐infusion arm. However, improvement in MDS‐UPDRS‐III was seen across all treatment arms. Adverse events were mild and transient. Conclusions: Three infusions of 10 × 10 ⁶ allo‐hMSCs/kg improved motor function in mild‐to‐moderate PwP, while two infusions showed less improvement than placebo. To address this discrepancy, future studies should conduct functional potency assays to understand batch‐to‐batch variability affecting clinical efficacy. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Lewy Body Disease (LBD) and Multiple System Atrophy (MSA) are synucleinopathies with distinct prognoses and neuropathologies, however, with overlapping clinical symptoms. Different disease characteristics are proposed to be determined by distinct conformations of alpha-synuclein (α-Syn) aggregates, which can self-propagate and spread between cells via a prion-like mechanism. The goal of this study is to investigate whether α-syn aggregates amplified from brain and CSF samples of LBD and MSA patients using the Seed Amplification Assay (SAA) maintain α-Syn seeding properties similar to those of α-syn aggregates derived from patients’ brains. To address this, SAA-amplified and un-amplified α-Syn aggregates from LBD and MSA patients’ brains, as well as SAA-amplified α-Syn aggregates from LBD and MSA patients’ CSF samples, were used to treat synuclein biosensor cells, and induced intracellular α-Syn inclusions were analyzed by confocal microscopy. Our data indicate that induced α-Syn aggregates from LBD and MSA patients’ brains have similar seeding properties and morphological characteristics in the α-Syn biosensor cells as those amplified from LBD and MSA patients’ brains, as well as those amplified from LBD and MSA patients’ CSF samples. In this study, we demonstrated that, regardless of the source of aggregates, the seeds from LBD and MSA produce cellular accumulation of α-Syn with distinct morphologies, confirming the presence of different conformational strains of α-Syn in LBD and MSA and allowing us to differentiate synucleinopathies based on the morphology of aggregates and seeding properties.

• Early differentiation between PD and atypical parkinsonism is challenging. • Variability in diagnosis can weaken statistical power in trials. • Precise diagnostic tools are needed for trial population homogeneity. • This patient initially diagnosed with PD, was diagnosed with MSA via CSF αSyn-SAA. • Adding αSyn-SAA to inclusion criteria could enhance subject selection in trials.