Alzheimer & Parkinson

With population aging, Alzheimer's disease (AD) is becoming increasingly prevalent, causing great health and economic burdens worldwide. Despite decades of research, there are still no effective disease-modifying treatments for AD, highlighting the urgent need for more in-depth understanding of the disease-causing mechanisms. The brain serotonin (5-HT) neurotransmission system undergoes structural and functional changes in aging and AD, which contributes to cognitive decline and comorbid mood...

Parkinson's disease is caused by the loss of dopamine neurons, causing motor symptoms. Initial cell therapies using fetal tissues showed promise but had complications and ethical concerns^(1-5). Pluripotent stem (PS) cells emerged as a promising alternative for developing safe and effective treatments⁶. In this phase I/II trial at Kyoto University Hospital, seven patients (ages 50-69) received bilateral transplantation of dopaminergic progenitors derived from induced PS (iPS) cells. Primary...

Parkinson's disease is a progressive neurodegenerative condition with a considerable health and economic burden¹. It is characterized by the loss of midbrain dopaminergic neurons and a diminished response to symptomatic medical or surgical therapy as the disease progresses². Cell therapy aims to replenish lost dopaminergic neurons and their striatal projections by intrastriatal grafting. Here, we report the results of an open-label phase I clinical trial (NCT04802733) of an investigational...

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Biobanks advance biomedical and clinical research by collecting and offering data and biological samples for numerous studies. However, the impact of these repositories varies greatly due to differences in their purpose, scope, governance, and data collected. Here, we computationally identified 2,663 biobanks and their textual mentions in 228,761 scientific articles, 16,210 grants, 15,469 patents, 1,769 clinical trials, and 9,468 public policy documents, helping characterize the academic...

The aggregation of α-synuclein (αSyn) is associated with Parkinson's disease and other related synucleinopathies. Considerable efforts have thus been directed at understanding this process. However, the recently discovered condensation pathway, which involves the formation of phase-separated liquid intermediate states, has added further complexity. In parallel, it has been reported that different αSyn splice isoforms may be implicated in aggregate formation in disease. In this study, we compare...

Widespread delivery of therapeutic proteins to the brain remains challenging. To determine whether human induced pluripotent stem cell (iPSC)-microglia (iMG) could enable brain-wide and pathology-responsive delivery of therapeutic cargo, we utilized CRISPR gene editing to engineer iMG to express the Aβ-degrading enzyme neprilysin under control of the plaque-responsive promoter, CD9. To further determine whether increased engraftment enhances efficacy, we utilized a CSF1R-inhibitor resistance...

Amyloid and tau proteins are important proteins in the pathological changes of Alzheimer's disease (AD), while Aβ pathology and tau pathology are the most critical factors contributing to the development of AD. Some studies have shown that there is a causal relationship between AD and diabetes mellitus, but there are no studies showing a causal relationship between diabetic traits and AD biomarkers, so further exploration is needed. We first summarized and analyzed the currently published...

Deep brain stimulation is a brain circuit intervention that can modulate distinct neural pathways for the alleviation of neurological symptoms in patients with brain disorders. In Parkinson's disease, subthalamic deep brain stimulation clinically mimics the effect of dopaminergic drug treatment, but the shared pathway mechanisms on cortex - basal ganglia networks are unknown. To address this critical knowledge gap, we combined fully invasive neural multisite recordings in patients undergoing...

Selective elimination of early pathological TAU species may be a promising therapeutic strategy to reduce the accumulation of TAU, which contributes to neurodegeneration and is a hallmark of Alzheimer's disease (AD). Pathological hyper-phosphorylated TAU can be degraded through selective autophagy, and NDP52/CALCOCO2 is one of the autophagy receptors involved in this process. In 2021, we discovered a variant of NDP52, called NDP52^(GE) (rs550510), that is more efficient at promoting autophagy....

This pioneering genome-wide association study examined surrogate markers for insulin resistance (IR) in 147,880 Taiwanese individuals using data from the Taiwan Biobank. The study focused on two IR surrogate markers: the triglyceride to high-density lipoprotein cholesterol (TG:HDL-C) ratio and the TyG index (the product of fasting plasma glucose and triglycerides). We identified genome-wide significance loci within four gene clusters: GCKR, MLXIPL, APOA5, and APOC1, uncovering 197 genes...

Alzheimer disease (AD) is a life-limiting neurodegenerative disorder that disproportionately affects women. Indeed, sex and gender are emerging as crucial modifiers of diagnostic and therapeutic pathways in AD. This Review provides an overview of the interactions of sex and gender with important developments in AD and offers insights into priorities for future research to facilitate the development and implementation of personalized approaches in the shifting paradigm of AD care. In particular,...