ArticleNature communications2022
Experimental evidence for temporal uncoupling of brain Aβ deposition and neurodegenerative sequelae.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Magnetic resonance microscopy maps widespread effects of Alzheimer's disease on brain structures and behavior in mice.Nature neuroscience · 2026Article
- New Perspective: Bench to Bedside Evidence of the Role of CD8+ T Cells in Alzheimer's Disease.Immunity, inflammation and disease · 2026Review
- Acute targeting of N-terminal tau protein has long-lasting beneficial effects in Tg2576 APP/Aβ mouse model by reducing cognitive impairment, cerebral Aβ-amyloidosis, synaptic remodeling and microgliosis later in life.Acta neuropathologica communications · 2025Article
- Immunotherapy against tau fragment diminishes AD pathology, improving synaptic function and cognition.Molecular neurodegeneration · 2025Article
- Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer's disease.Nature communications · 2024Observational
- Trial Analysis of Brain Activity Information for the Presymptomatic Disease Detection of Rheumatoid Arthritis.Bioengineering (Basel, Switzerland) · 2024Article
- Examining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Intracerebral inoculation of healthy non-transgenic rats with a single aliquot of oligomeric amyloid-β (1-42) profoundly and progressively alters brain function throughout life.Frontiers in aging neuroscience · 2024Article
- Advanced structural brain aging in preclinical autosomal dominant Alzheimer disease.Molecular neurodegeneration · 2023Article
- 14-3-3Journal of neuroinflammation · 2023Article
- Review
- Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer's disease.Nature medicine · 2023Article
- Effects of sleep deprivation on cognition and synaptic associated proteins in rodents: A systematic review and meta-analysis.Journal of Alzheimer's disease reportsReview
Corrections and comments
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Authors and funding
24 authors at 5 institutions in 4 countries.
Funding
Abstract
Brain Aβ deposition is a key early event in the pathogenesis of Alzheimer´s disease (AD), but the long presymptomatic phase and poor correlation between Aβ deposition and clinical symptoms remain puzzling. To elucidate the dependency of downstream pathologies on Aβ, we analyzed the trajectories of cerebral Aβ accumulation, Aβ seeding activity, and neurofilament light chain (NfL) in the CSF (a biomarker of neurodegeneration) in Aβ-precursor protein transgenic mice. We find that Aβ deposition increases linearly until it reaches an apparent plateau at a late age, while Aβ seeding activity increases more rapidly and reaches a plateau earlier, coinciding with the onset of a robust increase of CSF NfL. Short-term inhibition of Aβ generation in amyloid-laden mice reduced Aβ deposition and associated glial changes, but failed to reduce Aβ seeding activity, and CSF NfL continued to increase although at a slower pace. When short-term or long-term inhibition of Aβ generation was started at pre-amyloid stages, CSF NfL did not increase despite some Aβ deposition, microglial activation, and robust brain Aβ seeding activity. A dissociation of Aβ load and CSF NfL trajectories was also found in familial AD, consistent with the view that Aβ aggregation is not kinetically coupled to neurotoxicity. Rather, neurodegeneration starts when Aβ seeding activity is saturated and before Aβ deposition reaches critical (half-maximal) levels, a phenomenon reminiscent of the two pathogenic phases in prion disease.
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Registered trials
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