Observational studyJournal of Alzheimer's disease : JAD2019
An UNC5C Allele Predicts Cognitive Decline and Hippocampal Atrophy in Clinically Normal Older Adults.
Observational study in Journal of Alzheimer's disease : JAD, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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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
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- KL∗VS heterozygosity reduces brain amyloid in asymptomatic at-risk APOE∗4 carriers.Neurobiology of aging · 2021Pooled it
- The UNC5C T835M mutation associated with Alzheimer's disease leads to neurodegeneration involving oxidative stress and hippocampal atrophy in aged mice.Molecular neurodegeneration · 2025Article
- Netrin-1 signaling pathway mechanisms in neurodegenerative diseases.Neural regeneration research · 2025Article
- CSF Proteomics in Patients With Progressive Supranuclear Palsy.Neurology · 2024Article
- An Alzheimer's disease risk variant in TTC3 modifies the actin cytoskeleton organization and the PI3K-Akt signaling pathway in iPSC-derived forebrain neurons.Neurobiology of aging · 2023Article
- Interactions between genes involved in physiological dysregulation and axon guidance: role in Alzheimer's disease.Frontiers in genetics · 2023Article
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundThe UNC5C rs3846455G allele has been linked to poor cognitive resilience against age-related neuropathologies, but this association remains to be replicated, and the allele's effect on hippocampal neurodegeneration needs to be examined.
objectiveTo further validate the association between rs3846455G and faster cognitive decline, especially among cognitively normal older adults, and to assess whether rs3846455G predicts accelerated hippocampal volume loss in older adults.
methodsWe assessed participants in the Harvard Aging Brain Study (HABS), a longitudinal cohort study of older adults who were clinically normal at baseline. To avoid bias from population admixture, analyses were limited to participants of European descent with longitudinal neuroimaging data (n = 174). Linear mixed effect models were used to examine the effect of rs3846455G on longitudinal change of the Preclinical Alzheimer Cognitive Composite (PACC) and MRI-measured bilateral hippocampal volume, adjusting for baseline amyloid-β (Aβ) measured by the cortical Pittsburgh Compound B PET distributed volume ratio. We also tested whether hippocampal atrophy mediates the association between rs3846455G and greater PACC decline through a mediation analysis.
resultsrs3846455G was associated with greater PACC decline (β= -0.087/year, 95% CI -0.169 to -0.005, p = 0.039) after controlling for baseline Aβ. Further, rs3846455G predicted accelerated hippocampal atrophy after controlling for baseline Aβ (β= -57.3 mm3/year, 95% CI -102.8 to -11.9, p = 0.014). The association between rs3846455G and greater PACC decline was partially mediated by accelerated hippocampal atrophy (mediated effect (relative scale) = -0.014, 95% CI -0.032 to -6.0×10-4, p = 0.039).
conclusionUNC5C rs3846455G predicts greater cognitive decline and accelerated hippocampal atrophy in clinically normal older adults.
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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.