ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
Cognitively healthy centenarians are genetically protected against Alzheimer's disease.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07356700 (Deciphering the Factors of Longevity Through a Multi-Omics Study in Long-Lived Individuals in Hong Kong), which is not on this map. Cited by 38 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.
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.
Deciphering the Factors of Longevity Through a Multi-Omics Study in Long-Lived Individuals in Hong Kong
Who cites it
38 citing papers in PubMed, 43 citations in OpenAlex.
- TMEM106B is a selective modulator of TDP-43 pathology in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- TACR3 variant confers resilience to aging and Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- Human microglial transitions at the Aβ-tau inflection point associate with divergent pathways to dementia and resilience.Nature medicine · 2026Article
- Neocortical tau burden determines the degree of cognitive impairment in individuals with Braak stage V neurofibrillary degeneration.Acta neuropathologica · 2026Article
- TMEM106B C-terminal fragments drive nucleocytoplasmic transport failure and TDP-43 mislocalization in the aging human brain.bioRxiv : the preprint server for biology · 2026Article
- Imaging-genetics-based dementia risk prediction using deep survival neural networks in the Rotterdam Study.Scientific reports · 2026Article
- Article
- Neurodegeneration risk variants promote lysosomal TMEM106B fibril accumulation.bioRxiv : the preprint server for biology · 2026Article
- Immune dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2026Review
- The association of Alzheimer's disease-related SNPs with mild cognitive impairment susceptibility in the Chinese population.Scientific reports · 2026Article
- PLCG2 across human disease: genetic variants, signaling mechanisms, and clinical implications.Journal of translational medicine · 2026Review
- DNA methylation signature of cognitive reserve moderates CSF tau pathology in prodromal Alzheimer's disease.Research square · 2026Article
- Preserved cognitive-functional phenotype in centenarians and its association with modifiable risk factors for dementia: Results from the Colombian centenarians project.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Delivering Progranulin to Astrocytic Lysosomes Promotes Growth of Co-Cultured Neurons.Journal of neurochemistry · 2025Article
- Primary age-related tauopathy.Acta neuropathologica · 2025Review
- Alzheimer's disease-associated PLCG2 variants alter microglial state and function in human induced pluripotent stem cell-derived microglia-like cells.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Imaging-genetics-based dementia risk prediction using deep survival neural networks in the Rotterdam Study.Research square · 2025Article
- Polyunsaturated fatty acids, APOE genotypes, and dementia incidence and mortality among hypertensive adults.The journal of prevention of Alzheimer's disease · 2025Article
- Angiopoietin signalling is a central axis of amyloid-driven vascular dysfunction in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Exploring the Impact of Bioactive Compounds Found in Extra Virgin Olive Oil on NRF2 Modulation in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2025Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundAlzheimer's disease (AD) prevalence increases with age, yet a small fraction of the population reaches ages > 100 years without cognitive decline. We studied the genetic factors associated with such resilience against AD.
methodsGenome-wide association studies identified 86 single nucleotide polymorphisms (SNPs) associated with AD risk. We estimated SNP frequency in 2281 AD cases, 3165 age-matched controls, and 346 cognitively healthy centenarians. We calculated a polygenic risk score (PRS) for each individual and investigated the functional properties of SNPs enriched/depleted in centenarians.
resultsCognitively healthy centenarians were enriched with the protective alleles of the SNPs associated with AD risk. The protective effect concentrated on the alleles in/near ANKH, GRN, TMEM106B, SORT1, PLCG2, RIN3, and APOE genes. This translated to >5-fold lower PRS in centenarians compared to AD cases (P = 7.69 × 10 DISCUSSION: Maintaining cognitive health until extreme ages requires complex genetic protection against AD, which concentrates on the genes associated with the endolysosomal and immune systems. HIGHLIGHTS: Cognitively healthy cent enarians are enriched with the protective alleles of genetic variants associated with Alzheimer's disease (AD). The protective effect is concentrated on variants involved in the immune and endolysosomal systems. Combining variants into a polygenic risk score (PRS) translated to > 5-fold lower PRS in centenarians compared to AD cases, and ≈ 2-fold lower compared to middle-aged healthy controls.
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