ArticleAnnals of neurology2021
Onset of Preclinical Alzheimer Disease in Monozygotic Twins.
Article in Annals of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Cerebrospinal Fluid Amyloid and Tau Biomarker Changes Across the Alzheimer Disease Clinical Spectrum.JAMA network open · 2025Article
- Contributions of amyloid beta and cerebral small vessel disease in clinical decline.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The heritability of blood-based biomarkers related to risk of Alzheimer's disease in a population-based sample of early old-age men.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Genetically identical twin-pair difference models support the amyloid cascade hypothesis.Brain : a journal of neurology · 2023Article
- A Rare Case of Postoperative Encephalopathy in Twin.Cureus · 2023Article
- Rate of tau propagation is a heritable disease trait in genetically diverse mouse strains.iScience · 2023Article
- Histone Modifications in Alzheimer's Disease.Genes · 2023Review
- Plasma biomarkers predict amyloid pathology in cognitively normal monozygotic twins after 10 years.Brain communications · 2023Article
- CSF-Targeted Proteomics Indicate Amyloid-Beta Ratios in Patients with Alzheimer's Dementia Spectrum.International journal of Alzheimer's disease · 2023Article
- Genetically identical twins show comparable tau PET load and spatial distribution.Brain : a journal of neurology · 2022Article
- A genetically modified minipig model for Alzheimer's disease with SORL1 haploinsufficiency.Cell reports. Medicine · 2022Article
- P-tau subgroups in AD relate to distinct amyloid production and synaptic integrity profiles.Alzheimer's research & therapy · 2022Article
- Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer's disease.Molecular neurodegeneration · 2022Article
- Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study.Alzheimer's & dementia (New York, N. Y.) · 2022Article
- Impact of maternal gestational weight gain in twin pregnancies on early childhood obesity risk: A longitudinal birth cohort study.Frontiers in pediatrics · 2022Article
- CSF Proteomic Alzheimer's Disease-Predictive Subtypes in Cognitively Intact Amyloid Negative Individuals.Proteomes · 2021Article
- Roles and Mechanisms of Gut Microbiota in Patients With Alzheimer's Disease.Frontiers in aging neuroscience · 2021Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe present work was undertaken to study the genetic contribution to the start of Alzheimer's disease (AD) with amyloid and tau biomarkers in cognitively intact older identical twins.
methodsWe studied in 96 monozygotic twin-pairs relationships between amyloid-beta (Aβ) aggregation as measured by the Aβ1-42/1-40 ratio in cerebrospinal fluid (CSF; n = 126) and positron emission tomography (PET, n = 194), and CSF markers for Aβ production (beta-secretase 1, Aβ1-40, and Aβ1-38) and CSF tau. Associations among markers were tested with generalized estimating equations including a random effect for twin status, adjusted for age, gender, and apolipoprotein E ε4 genotype. We used twin analyses to determine relative contributions of genetic and/or environmental factors to AD pathophysiological processes.
resultsTwenty-seven individuals (14%) had an abnormal amyloid PET, and 14 twin-pairs (15%) showed discordant amyloid PET scans. Within twin-pairs, Aβ production markers and total-tau (t-tau) levels strongly correlated (r range = 0.73-0.86, all p < 0.0001), and Aβ aggregation markers and 181-phosphorylated-tau (p-tau) levels correlated moderately strongly (r range = 0.50-0.64, all p < 0.0001). Cross-twin cross-trait analysis showed that Aβ1-38 in one twin correlated with Aβ1-42/1-40 ratios, and t-tau and p-tau levels in their cotwins (r range = -0.28 to 0.58, all p < .007). Within-pair differences in Aβ production markers related to differences in tau levels (r range = 0.49-0.61, all p < 0.0001). Twin discordance analyses suggest that Aβ production and tau levels show coordinated increases in very early AD.
interpretationOur results suggest a substantial genetic/shared environmental background contributes to both Aβ and tau increases, suggesting that modulation of environmental risk factors may aid in delaying the onset of AD pathophysiological processes. ANN NEUROL 2021;89:987-1000.
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