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Alzheimer & Parkinson

Hippocampal neural stem cell exosomes promote brain resilience against the impact of tau oligomers

3 weeks 5 days ago
A promising therapeutic intervention for preventing the onset and progression of Alzheimer's Disease (AD) is to protect and improve synaptic resilience, a well-established early vulnerability associated with the toxic effects of oligomers of Aβ (AβO) and Tau (TauO). We have previously reported that exosomes from hippocampal neural stem cells (NSCs) protect synapses against AβO. Here, we demonstrate how exosomes can also shield against TauO toxicity in adult mice synapses, potentially benefiting...
Balaji Krishnan

Microglial mechanisms drive amyloid-beta clearance in immunized patients with Alzheimer's disease

3 weeks 5 days ago
Alzheimer's disease (AD) therapies utilizing amyloid-β (Aβ) immunization have shown potential in clinical trials. Yet, the mechanisms driving Aβ clearance in the immunized AD brain remain unclear. Here, we use spatial transcriptomics to explore the effects of both active and passive Aβ immunization in the AD brain. We compare actively immunized patients with AD with nonimmunized patients with AD and neurologically healthy controls, identifying distinct microglial states associated with Aβ...
Lynn van Olst

Astrocyte glypican 5 regulates synapse maturation and stabilization

3 weeks 5 days ago
The maturation and stabilization of appropriate synaptic connections is a vital step in neural circuit development; however, the molecular signals underlying these processes are not fully understood. We show that astrocytes, through production of glypican 5 (GPC5), are required for maturation and refinement of synapses in the mouse cortex during the critical period. In the absence of astrocyte GPC5, thalamocortical synapses show structural immaturity, including smaller presynaptic terminals,...
Alexandra P Bosworth

Phosphorylated tau 181 and 217 are elevated in serum and muscle of patients with amyotrophic lateral sclerosis

3 weeks 6 days ago
Blood phosphorylated (p)-tau 181 and p-tau 217 have been proposed as accurate biomarkers of Alzheimer's disease (AD) pathology. However, blood p-tau 181 is also elevated in amyotrophic lateral sclerosis (ALS) without a clearly identified source. We measured serum p-tau 181 and p-tau 217 in a multicentre cohort of ALS (n = 152), AD (n = 111) cases and disease controls (n = 99) recruited from four different centres. Further, we investigated the existence of both p-tau species using...
Samir Abu-Rumeileh

Tau filaments with the Alzheimer fold in human MAPT mutants V337M and R406W

3 weeks 6 days ago
Frontotemporal dementia (FTD) and Alzheimer's disease (AD) are the most common forms of early-onset dementia. Unlike AD, FTD begins with behavioral changes before the development of cognitive impairment. Dominantly inherited mutations in MAPT, the microtubule-associated protein tau gene, give rise to cases of FTD and parkinsonism linked to chromosome 17. These individuals develop abundant filamentous tau inclusions in brain cells in the absence of β-amyloid deposits. Here, we used cryo-electron...
Chao Qi

Sex differences in age-associated neurological diseases-A roadmap for reliable and high-yield research

3 weeks 6 days ago
Once taken into consideration, sex differences in neurological diseases emerge in abundance: (i) Stroke severity is significantly higher in females than in males, (ii) Alzheimer's disease (AD) pathology is more pronounced in females, and (iii) conspicuous links with hormonal cycles led to female-specific diagnoses, such as catamenial migraines and epilepsy. While these differences receive increasing attention in isolation, they likely link to similar processes in the brain. Hence, this review...
Anna K Bonkhoff

The interplay between age at menopause and synaptic integrity on Alzheimer's disease risk in women

3 weeks 6 days ago
Menopause is a major biological transition that may influence women's late-life brain health. Earlier estrogen depletion-via earlier menopause-has been associated with increased risk for Alzheimer's disease (AD). Synaptic dysfunction also incites and exacerbates AD progression. We investigated whether age at menopause and synaptic health together influence AD neuropathology and cognitive trajectories using clinical and autopsy data from 268 female decedents in the Rush Memory and Aging Project....
Madeline Wood Alexander

Associations between hormone therapy use and tau accumulation in brain regions vulnerable to Alzheimer's disease

3 weeks 6 days ago
Elucidating the downstream impact of exogenous hormones on the aging brain will have far-reaching consequences for understanding why Alzheimer's disease (AD) predominates in women almost twofold over men. We tested the extent to which menopausal hormone therapy (HT) use is associated with later-life amyloid-β (Aβ) and tau accumulation using PET on N = 146 baseline clinically normal women, aged 51 to 89 years. Women were scanned over a 4.5-year (SD, 2.1; range, 1.3 to 10.4) and 3.5-year (SD, 1.5;...
Gillian T Coughlan

Deep learning-based cell-specific gene regulatory networks inferred from single-cell multiome data

4 weeks ago
Gene regulatory networks (GRNs) provide a global representation of how genetic/genomic information is transferred in living systems and are a key component in understanding genome regulation. Single-cell multiome data provide unprecedented opportunities to reconstruct GRNs at fine-grained resolution. However, the inference of GRNs is hindered by insufficient single omic profiles due to the characteristic high loss rate of single-cell sequencing data. In this study, we developed scMultiomeGRN, a...
Junlin Xu

A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models

4 weeks 1 day ago
This systematic review sought to assess the impact of nicotinamide adenine dinucleotide (NAD^(+)) precursors on cognitive impairments in several diseases in rat/mouse models. Accumulating evidence suggests that inflammation, apoptosis, oxidative stress responses, and mitochondrial dysfunction are potential factors of cognitive deficits in aging, Alzheimer's disease (AD), diabetes, traumatic brain injury (TBI), vascular dementia (VAD), and schizophrenia. NAD^(+) precursors have received increased...
Musaab Abdulrazzaq Qader

Zipper-interacting protein kinase mediates neuronal cell death and cognitive dysfunction in traumatic brain injury via regulating DEDD

4 weeks 1 day ago
Neuronal cell death is a causative process in traumatic brain injury (TBI)-induced structural and functional impairment of the central nervous system. However, the upstream trigger of TBI-induced neuronal loss and the underlying molecular pathways remain unclear. Zipper-interacting protein kinase (ZIPK) has been shown to be upregulated in Alzheimer's disease and ischemic stroke and to play a role in cellular apoptosis, while its pathological significance in TBI has not been reported. Herein, we...
Yingxue Mei

Long-read RNA sequencing atlas of human microglia isoforms elucidates disease-associated genetic regulation of splicing

4 weeks 1 day ago
Microglia, the innate immune cells of the central nervous system, have been genetically implicated in multiple neurodegenerative diseases. Mapping the genetics of gene expression in human microglia has identified several loci associated with disease-associated genetic variants in microglia-specific regulatory elements. However, identifying genetic effects on splicing is challenging because of the use of short sequencing reads. Here, we present the isoform-centric microglia genomic atlas...
Jack Humphrey

Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases

4 weeks 1 day ago
Protein aggregation is a hallmark of neurodegenerative diseases, which connects these neuropathologies by a common phenotype. Various proteins and peptides form aggregates that are poorly degraded, and their ensuing pathological accumulation underlies these neurodegenerative diseases. Similarities may exist in the mechanisms responsible for the buildup of these aggregates. Therefore, therapeutics designed to treat one neurodegenerative disease may be beneficial to others. In ALS models, the...
Elizabeth A Johnson
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