Biomedical Research Networking Center on Neurodegenerative Diseases

Deep phenotyping of white matter tissue composition in dementia with Lewy bodies

Abstract Background White matter signal abnormalities (WMSA) on MRI are common in dementia with Lewy bodies (DLB), and more severe WMSA have been associated with increased neurodegeneration in DLB. However, the underlying mechanisms of WMSA remain unclear. Single-Shell 3-Tissue C...

From Platform Development to Scale-Up: Stable Producer Cell Line-Based Lentiviral Vector Manufacturing

Background: The development of stable producer cell lines (SCLs) represents a promising alternative for lentiviral vector (LVV) manufacturing, offering improved reproducibility and reduced manufacturing costs. In previous work, our group established an SCL generation platform bas...

Blood-brain barrier opening with focused ultrasound reduces neuromelanin in a non-human primate model.

Age-related accumulation of neuromelanin (NM) has been implicated in the intrinsic vulnerability of catecholaminergic neurons in Parkinson's disease. Postmortem studies in Parkinson's disease patients have revealed elevated intracellular and extracellular NM in the substantia nig...

Cognitive vergence and pupil response during oddball task are associated with Alzheimer´s disease cerebrospinal fluid neurodegenerative biomarkers

Alzheimer’s disease (AD) can be diagnosed using cerebrospinal fluid (CSF) biomarkers reflecting amyloid and tau pathology. However, they provide no information about functional network status. We aimed to determine whether CSF biomarkers (Aβ42, p-Tau, t-Tau, and Aβ42/p-Tau ratio)...

Regional differences in dendritic spine morphology and innervation of the trisynaptic circuit of a mouse model of GSK-3β overexpression

Abstract The trisynaptic circuit, which includes the entorhinal cortex (EC), dentate gyrus (DG), and Cornu Ammonis (CA1, CA2, and CA3) of the hippocampus, is among the regions first affected by Alzheimer’s disease (AD). Glycogen synthase kinase-3β (GSK-3β) has emerged as a key en...

Validation of plasma core biomarkers of Alzheimer's disease: A multicenter study in usual practice conditions

Background The new anti-amyloid therapies have brought the challenge of early and feasible identification of Alzheimer's disease (AD). Plasma biomarkers are promising tools, but real-world evidence remains limited. Objective We aimed to evaluate the diagnostic performance of plas...

Plasma Aβ42/Aβ40 predicts longitudinal amyloid pathology and clinical progression in amyloid-PET negative individuals with subjective cognitive decline

Early detection of amyloid-β (Aβ) pathology is critical for timely intervention in Alzheimer’s disease (AD). Changes in plasma Aβ42/Aβ40 levels appear early in the AD continuum, but whether they precede amyloid deposition detected by Aβ-PET requires further research. Data from 16...

Oveporexton for Narcolepsy Type 1 — Results from Two Phase 3 Trials

BACKGROUND: Narcolepsy type 1 is characterized by excessive daytime sleepiness, cataplexy, disrupted sleep, sleep paralysis, and hypnagogic or hypnopompic hallucinations. Oveporexton (TAK-861), an oral orexin receptor 2-selective agonist, reduced symptoms of narcolepsy type 1 in...

The Parkinsonian Motor Spectrum in Nonagenarians: A Population‐Based Study

BACKGROUND: Population-based data on mild parkinsonian signs (MPS) and parkinsonism in nonagenarians are scarce. OBJECTIVES: To estimate the prevalence of MPS, definite parkinsonism, and broader parkinsonian motor phenotypes; assess MPS after excluding idiopathic Parkinson diseas...

From feasibility to neuroanatomic validity of remote cognitive smartphone assessments in early Alzheimer’s disease

ABSTRACT Digital health technologies (DHT) offer a promising solution to the timely identification of early Alzheimer’s disease (eAD) to enable early treatment. This study evaluated the feasibility, acceptability, adherence, reliability, and preliminary clinical and content valid...

Population-based cohort study of modifiable risk factors for dementia and Alzheimer disease mortality in Spain

Abstract Background Although many modifiable factors are linked to dementia risk, their association with dementia and Alzheimer disease (AD) mortality remains unclear. We aimed to identify late-life modifiable factors associated with these outcomes and assess sex differences. Met...

Cognitive vergence and pupillary responses as functional oculomotor signatures to differentiate AT(N) biological profiles in older adults with mild cognitive impairment

Abstract The locus coeruleus (LC), the earliest site of tau accumulation in Alzheimer’s disease, directly influences pupillary and vergence oculomotor systems. Whether task-evoked oculomotor dynamics can non-invasively differentiate AT(N) profiles, A+T+ (biological Alzheimer’s di...

Cell Type‐Specific Extracellular Vesicles in Mouse Brain: Proteomic Signatures Highlight Astrocytic GlialCAM Network and GPCR Enrichment

Extracellular vesicles (EVs) mediate intercellular communication in the central nervous system (CNS) and are emerging as biomarkers of brain health and disease. However, the molecular composition of cell type-specific brain EVs, particularly astrocyte-derived EVs (ADEVs), remains...

PLCG2 downregulation impairs synaptic function and increases Alzheimer’s disease hallmarks in neuronal cultures

We developed a high-content screening to investigate how Alzheimer’s disease (AD) genetic risk factors may affect synaptic mechanisms in rat primary neuronal cultures. Of the target genes identified, we found that Plcg2 downregulation in mouse dentate gyrus neurons consistently d...

Data-driven mapping of known and novel fluid biomarker progression profiles in genetic frontotemporal lobar degeneration

Abstract Introduction Recent proteomic studies have identified both established and novel proteins in genetic frontotemporal lobar degeneration (FTLD). However, it remains unclear at what point in the disease these proteins deviate from normal levels and how their trajectories re...

Burden, perception of stigma, and gender differences among informal care partners of individuals with mild cognitive impairment

Background Caring for individuals with mild cognitive impairment (MCI) is increasingly recognized as a significant clinical challenge. However, the latent burden, driven by perceived stigma and gender-specific vulnerabilities, remains poorly characterized during these early stage...

Circulating MMP-7 is associated with cognitive decline in individuals with vascular risk factors

Background Vascular risk factors contribute substantially to late-life cognitive impairment and interact with neurodegenerative processes underlying dementia. Blood–brain barrier (BBB) dysfunction has emerged as a key mechanism linking vascular pathology to cognitive decline; how...