ReviewActa neuropathologica2019
The new genetic landscape of Alzheimer's disease: from amyloid cascade to genetically driven synaptic failure hypothesis?
Review in Acta neuropathologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.
- Microglial Phagocytosis: A Disease-Associated Process Emerging from Alzheimer's Disease Genetics.Trends in neurosciences · 2020Pooled it
- Cell-based polygenic risk scores predict clinical progression and prioritize network-based therapeutic targets in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Genetic and pathway complexity in Alzheimer's disease: Insights from multi-omic data about the immune response and mitochondrial function.Neural regeneration research · 2026Article
- The potential and therapeutic advances of the integrin family in neurological disorders.Neural regeneration research · 2026Article
- BIN1 gain-of-function in the presynaptic compartment leads to isoform-specific synaptotoxicity.Alzheimer's research & therapy · 2026Article
- Review
- Integrated computational, pharmacological and molecular investigations of piperitone in mitigating Alzheimer disease pathology by targeting cholinesterases, β-secretase and neuroinflammation.Inflammopharmacology · 2026Article
- Immuno-Regulation of Brain Region-Specific Organoids Containing Isogenic Microglia-Like Cells.Advanced healthcare materials · 2026Article
- Chronic methanol exposure induces cognitive impairment and Alzheimer's-like pathology in rhesus monkeys.Animal models and experimental medicine · 2026Article
- Stratification of brain-derived extracellular vesicles of Alzheimer's disease patients indicates a unique proteomic content and a higher seeding capacity of small extracellular vesicles.Translational neurodegeneration · 2025Article
- The emerging role of circular RNAs in neuropsychiatric disorders.Translational psychiatry · 2025Review
- Alzheimer's disease multi-ancestry genome-wide interaction and stratified study with smoking.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Long-read sequencing identifies ATXN3 repeat expansions, and transcriptomics reveals disease progression biomarkers and druggable targets for spinocerebellar ataxia type 3.BMC neurology · 2025Article
- Clinical Significance of APOE4 Genotyping: Potential for Personalized Therapy and Early Diagnosis of Alzheimer's Disease.Journal of clinical medicine · 2025Review
- Associations between dementia and exposure to topical glaucoma medications.Journal of Alzheimer's disease : JAD · 2025Article
- Synapse vulnerability and resilience underlying Alzheimer's disease.EBioMedicine · 2025Review
- Non-Drug and Non-Invasive Therapeutic Options in Alzheimer's Disease.Biomedicines · 2025Review
- The structure of an amyloid precursor protein/talin complex indicates a mechanical basis of Alzheimer's disease.Open biology · 2024Article
- Network dynamics-based subtyping of Alzheimer's disease with microglial genetic risk factors.Alzheimer's research & therapy · 2024Article
- Review on anti-alzheimer drug development: approaches, challenges and perspectives.RSC advances · 2024Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A strong genetic predisposition (60-80% of attributable risk) is present in Alzheimer's disease (AD). In view of this major genetic component, identification of the genetic risk factors has been a major objective in the AD field with the ultimate aim to better understand the pathological processes. In this review, we present how the genetic risk factors are involved in APP metabolism, β-amyloid peptide production, degradation, aggregation and toxicity, innate immunity, and Tau toxicity. In addition, on the basis of the new genetic landscape, resulting from the recent high-throughput genomic approaches and emerging neurobiological information, we propose an over-arching model in which the focal adhesion pathway and the related cell signalling are key elements in AD pathogenesis. The core of the focal adhesion pathway links the physiological functions of amyloid precursor protein and Tau with the pathophysiological processes they are involved in. This model includes several entry points, fitting with the different origins for the disease, and supports the notion that dysregulation of synaptic plasticity is a central node in AD. Notably, our interpretation of the latest data from genome wide association studies complements other hypotheses already developed in the AD field, i.e., amyloid cascade, cellular phase or propagation hypotheses. Genetically driven synaptic failure hypothesis will need to be further tested experimentally within the general AD framework.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.