ArticleEuropean journal of neurology2022
APOE ε4 influences cognitive decline positively in APP and negatively in PSEN1 mutation carriers with autosomal-dominant Alzheimer's disease.
Article in European journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 8 citations in OpenAlex.
- APOE and genetic risk variants influence Alzheimer's disease onset in carriers of an extra copy of APP, with and without Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Amyloid-Frontiers in aging neuroscience · 2026Article
- CTAD taskforce: genetic therapies in Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Review
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- Pathological Functions of Lysosomal Ion Channels in the Central Nervous System.International journal of molecular sciences · 2024Review
- Early- and Late-Onset Alzheimer's Disease: Two Sides of the Same Coin?Diseases (Basel, Switzerland) · 2024Review
- Potential Modifying Effect of theInternational journal of molecular sciences · 2023Article
- Effect of apolipoprotein genotype and educational attainment on cognitive function in autosomal dominant Alzheimer's disease.Nature communications · 2023Article
- APOE ε4 influences cognitive decline positively in APP and negatively in PSEN1 mutation carriers with autosomal-dominant Alzheimer's disease.European journal of neurology · 2022Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe aim was to investigate the effect of APOE ε4 allele on cognitive decline in adAD. Presence of the APOE ε4 allele reduces age of symptom onset, increases disease progression, and lowers cognitive performance in sporadic Alzheimer's disease (AD), while the impact of the APOE ε4 allele in autosomal-dominant AD (adAD) is incompletely known.
methodsMutation carriers (MCs; n = 39) and non-carriers (NCs; n = 40) from six adAD families harbouring a mutation in the APP (28 MCs and 25 NCs) or the PSEN1 genes (11 MCs and 15 NCs) underwent repeated cognitive assessments. A timeline of disease course was defined as years to expected age of clinical onset (YECO) based on history of disease onset in each family. The MC and NC groups were comparable with regard to demographics and prevalence of the APOE ε4 allele. The relationship between cognitive decline and YECO, YECO
resultsThe trajectory of cognitive decline was significantly predicted by linear and quadratic YECO and education in MCs and was determined by age and education in NCs. Adding APOE ε4 allele (presence/absence) as a predictor did not change the results in the MC and NC groups. The outcome also remained the same for MCs and NCs after adding the APOE-by-YECO interaction as a predictor. Analyses of APP and PSEN1 MCs separately showed favourable APOE-by-YECO interaction in APP (less steep decline) and unfavourable interaction in PSEN1 (steeper decline), linked to the APOE ε4 allele.
conclusionThe APOE ε4 allele influences cognitive decline positively in APP and negatively in PSEN1 mutation carriers with adAD, indicating a possible antagonistic pleiotropy.
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