Skip to main content

Alzheimer & Parkinson

Differences in patterns of functional and structural connectivity alterations of hippocampal subregions in patients on the Alzheimer's disease spectrum

20 hours 45 minutes ago
The present study was conducted to construct structure connectivity (SC) and functional connectivity (FC) between different hippocampal subregions and the whole brain based on structural and function Magnetic Resonance Imaging, and to explore the changes in hippocampal subregions structural and functional connectivity in the different stages of Alzheimer's Disease (AD). 117 participants (75 female, 42 male) aged 60-88 years were recruited from the Sino-Longitudinal Study on Cognitive Decline in...
Lianghui Ni

Machine learning in Alzheimer's disease genetics

1 day 20 hours ago
Traditional statistical approaches have advanced our understanding of the genetics of complex diseases, yet are limited to linear additive models. Here we applied machine learning (ML) to genome-wide data from 41,686 individuals in the largest European consortium on Alzheimer's disease (AD) to investigate the effectiveness of various ML algorithms in replicating known findings, discovering novel loci, and predicting individuals at risk. We utilised Gradient Boosting Machines (GBMs), biological...
Matthew Bracher-Smith

Amyloid-lowering immunotherapies for Alzheimer disease: current status and future directions

1 day 20 hours ago
The treatment of Alzheimer disease (AD) has crossed a pivotal threshold, marked by the landmark approvals of the first-ever disease-modifying therapies. These immunotherapies, specifically monoclonal antibodies (mAbs) that target various amyloid-β (Aβ) species including proto-fibrillar and fibrillar forms, substantially lower levels of Aβ in the brain. The therapies have collectively demonstrated the ability to slow cognitive and clinical decline in large placebo-controlled trials, ushering a...
Michael S Rafii

PPM1M, an LRRK2-counteracting, phosphoRab12-preferring phosphatase with a potential link to Parkinson's disease

1 day 20 hours ago
Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of Rab GTPases that regulate receptor trafficking, and LRRK2-activating mutations are linked to Parkinson's disease. Rab phosphorylation is a transient event that can be reversed by phosphatases, including protein phosphatase, Mg2^(+)/Mn2^(+) dependent 1H (PPM1H), which acts on phosphorylated Rab 8A (phosphoRab8A) and phosphoRab10. Here, we report a phosphatome-wide small interfering RNA (siRNA) screen that identified PPM1M as a...
Claire Y Chiang

Personalised regional modelling predicts tau progression in the human brain

1 day 20 hours ago
Aggregation of the hyperphosphorylated tau protein is a central driver of Alzheimer's disease, and its accumulation exhibits a rich spatiotemporal pattern that unfolds during the course of the disease, sequentially progressing through the brain across axonal connections. It is unclear how this spatiotemporal process is orchestrated, namely, to what extent the spread of pathologic tau is governed by transport between brain regions, local production, or both. To address this, we develop a...
Pavanjit Chaggar

Enhanced focality and intensity in deep brain targeting: In silico study on multi-channel temporal interference stimulation for Parkinson's disease

2 days 20 hours ago
This study introduces a novel multi-channel temporal interference stimulation (M-TIS) paradigm and rigorously evaluates its capacity to non-invasively target the globus pallidus internus (GPi), a pivotal region in Parkinson's disease (PD) treatment. Employing realistic human head models derived from MRI data and sophisticated finite element modeling, we demonstrate that M-TIS achieves significantly enhanced stimulation intensity and focality within the GPi compared to conventional single-channel...
Bangyu Wang

Amyloid and tau pathologies cross-talk to promote Alzheimeŕs disease: novel mechanistic insights

3 days 20 hours ago
Aging-related declines in energy metabolism represent a key risk factor for the development of amyloid pathology, the earliest hallmark of Alzheimer's disease. Aging also contributes to the emergence of the second major hallmark, tau pathology, whose propagation is facilitated by pre-existing amyloid accumulation. The overlap of amyloid and tau pathologies ultimately leads to neurodegeneration and the onset of Alzheimer's disease-the most prevalent form of dementia. Recent findings underscore a...
Jesús Avila

Synaptic enrichment of pSer129 alpha-synuclein correlates with dopaminergic denervation in early-stage Parkinson's disease

4 days 20 hours ago
In Parkinson's disease (PD), α-synuclein aggregation in striatal synapses is hypothesised to trigger a cascade of events leading to synaptic loss and cortical Lewy body (LB) pathology. Using multiplex immunofluorescence and confocal microscopy on 69 brains spanning Braak stages 0-6-including controls, incidental LB disease (iLBD), and PD-we show that phosphorylated (pSer129) α-synuclein is enriched in putaminal dopaminergic synapses already in early disease stages, and associates with...
Irene Frigerio

Identifying people with potentially undiagnosed dementia with Lewy bodies using natural language processing

4 days 20 hours ago
Natural language processing (NLP) can expand the utility of clinical records data in dementia research. We deployed NLP algorithms to detect core features of dementia with Lewy bodies (DLB) and applied those to a large database of patients diagnosed with dementia in Alzheimer's disease (AD) or DLB. Of 14,329 patients identified, 4.3% had a diagnosis of DLB and 95.7% of dementia in AD. All core features were significantly commoner in DLB than in dementia in AD, although 18.7% of patients with...
Mohamed Heybe

CHI3L1/YKL-40 signaling inhibits neurogenesis in models of Alzheimer's disease

4 days 20 hours ago
CHI3L1/YKL-40 is an astrocyte-secreted glycoprotein recognized as a biomarker of CNS inflammation and implicated in Alzheimer's disease (AD) cognitive decline. However, its precise pathological role remains unclear. Here, we investigate CHI3L1's function and its therapeutic potential in AD using both human induced pluripotent stem cell-derived neurogenesis models and in vivo conditional AD mouse models, with astrocyte-specific CHI3L1 knockout, alongside 5XFAD mice. Our data reveal that CHI3L1...
Xin Yang

Insights into the toxic effects of micro-nano-plastics on the human brain and their relationship with the onset of neurological diseases: A narrative review

5 days 20 hours ago
The intensive production and use of plastics, poor biodegradability and inadequate recycling have caused excessive and alarming environmental pollution. This has led to the inevitable intake by humans, through different routes, of small plastic particles, the micro and nano-plastics (MNPs) with sizes ranging from nanometers (<1000 nm) to micrometers (from 5 mm to 1 µm). MNPs can cause harmful effects in human tissues and organs, contributing to the early onset of aging and various age-related...
Carmela Rita Balistreri

AI-guided patient stratification improves outcomes and efficiency in the AMARANTH Alzheimer's Disease clinical trial

5 days 20 hours ago
Alzheimer's Disease (AD) drug discovery has been hampered by patient heterogeneity, and the lack of sensitive tools for precise stratification. Here, we demonstrate that our robust and interpretable AI-guided tool (predictive prognostic model, PPM) enhances precision in patient stratification, improving outcomes and decreasing sample size for a AD clinical trial. The AMARANTH trial of lanabecestat, a BACE1 inhibitor, was deemed futile, as treatment did not change cognitive outcomes, despite...
Delshad Vaghari

Amyloid-β disrupts APP-regulated protein aggregation and dissociation from recycling endosomal membranes

5 days 20 hours ago
Secretory proteins aggregate into non-soluble dense-core granules in recycling endosome-like compartments prior to regulated release. By contrast, aberrantly processed, secreted amyloid-β (Aβ) peptides derived from amyloid precursor protein (APP) form pathological extracellular amyloidogenic aggregations in late-stage Alzheimer's disease (AD). By examining living Drosophila prostate-like secondary cells, we show that both APP and Aβ peptides affect normal biogenesis of dense-core granules. These...
Preman J Singh

Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease

5 days 20 hours ago
CONCLUSIONS: Using cross-population GWAS meta-analyses, we identify novel LOAD susceptibility loci in/near LRRC4C and LHX5-AS1, both with known roles in neuronal development, as well as several novel population-unique loci. Reflecting the power of diverse ancestry in GWAS, we detect the SHARPIN locus with only 13.7% of the sample size of the NHW GWAS study (n = 409,589) in which this locus was first observed. Continued expansion into larger multi-ancestry studies will provide even more power for...
Farid Rajabli

Alzheimer's genetic risk factor Bin1 controls synapse vesicle exo-endocytosis in inhibitory synapses

5 days 20 hours ago
BIN1, a late-onset Alzheimer's disease (LOAD) risk gene, is an endocytic regulator with an unclear synaptic function. We find Bin1 more prominently in inhibitory synapses (vGAT positive) than in excitatory ones (vGLUT1 positive). Bin1 knockdown reduces inhibitory synapses independently of Aβ42 production, increasing GABA release from the remaining synapses due to accelerated vGAT exocytosis and endocytosis, which decreases the size of inhibitory synaptic endosomes. In excitatory synapses, Bin1...
Mariana A Barata

Interpretable deep learning framework for understanding molecular changes in human brains with Alzheimer's disease: implications for microglia activation and sex differences

6 days 20 hours ago
The utilization of artificial intelligence in studying the dysregulation of gene expression in Alzheimer's disease (AD) affected brain tissues remains underexplored, particularly in delineating common and specific transcriptomic signatures across different brain regions implicated in AD-related cellular and molecular processes, which could help illuminate novel disease biology for biomarker and target discovery. Herein we developed a deep learning framework, which consisted of multi-layer...
Maitry Ronakbhai Trivedi

Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex

6 days 20 hours ago
Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive...
Rik Ossenkoppele

A genetically encoded selection for amyloid-β oligomer binders

1 week ago
Soluble amyloid-β oligomers (AβOs) are a hypothesized source of neurotoxicity in Alzheimer disease. Binding proteins that recognize these species may have high utility in diagnostic and therapeutic applications. However, identifying binders to AβOs directly generated from the aggregation cascade is challenging because of the short lifetime and low concentrations of oligomer populations. We report a strategy to detect binding to AβOs formed during Aβ42 aggregation using a genetically encoded...
ByungUk Lee
Checked
3 minutes 21 seconds ago
Alzheimer and Parkinson: Latest results from PubMed
Subscribe to Alzheimer & Parkinson feed