Phenotypic Characterization of Recently Identified PSEN1 Genetic Variants in ADAD in Colombia

Topic: Brain proteins, microglia and lab models

The sample included 61 participants (55.7% female), aged 18-58, with a median education of 12 years (IQR: 10-14). Of these, 77% were cognitively unimpaired (MMSE: 30, IQR: 29-30; CDR-SB: 0), 15% had mild cognitive impairment (MMSE: 25.1, SD: 3.6; CDR-SB: 1.9, SD: 1.1), and 8% had dementia (MMSE: 21, SD: 6.5; CDR-SB: 3.9, SD: 3.1). All symptomatic individuals exhibited primarily amnestic symptoms, and one carrier of the PSEN1-Pro284Leu variant presented motor signs. As expected-given that most participants were in preclinical stages-no statistically significant differences in clinical or cognitive features were observed across variants. Twenty-eight participants were in the primary prevention range (EYO: -11 to -35 years) and thirty-three in the secondary prevention range (EYO: -10 to +13 years). Parental age at onset differed by variant location: intramembranous (50 years, IQR: 46-53), cytoplasmic (40.5 years, SD: 4.6), and extracellular (45 years, IQR: 45-48). These findings are consistent with existing literature and underscore the value of characterizing preclinical ADAD cohorts, supported by biomarkers, to guide early diagnostic and therapeutic strategies, especially in the context of clinical trials. We expect to have complete fluid and neuroimaging biomarker and follow-up data for the presentation of these results.

@article{guerrero2025-41433957,
  author  = {Guerrero, Alejandro and Garcia‐Cifuentes, Elkin and Rodas-Marín, Jan Karlo and Baena, Ana Y. and Serna, Laura and Leon‐Varela, Yudy M and Duque, S Francisco Levi and Martínez, Juan F and others},
  title   = {{Phenotypic Characterization of Recently Identified PSEN1 Genetic Variants in ADAD in Colombia}},
  journal = {Alzheimer s \& Dementia},
  year    = {2025},
  doi     = {10.1002/alz70861_108984},
  pmid    = {41433957},
  url     = {https://doi.org/10.1002/alz70861_108984}
}

Key findings

• The sample included 61 participants (55.7% female), aged 18-58, with a median education of 12 years (IQR: 10-14).
• Of these, 77% were cognitively unimpaired (MMSE: 30, IQR: 29-30; CDR-SB: 0), 15% had mild cognitive impairment (MMSE: 25.1, SD: 3.6; CDR-SB: 1.9, SD: 1.1), and 8% had dementia (MMSE: 21, SD: 6.5; CDR-SB: 3.9, SD: 3.1).
• All symptomatic individuals exhibited primarily amnestic symptoms, and one carrier of the PSEN1-Pro284Leu variant presented motor signs.
• As expected-given that most participants were in preclinical stages-no statistically significant differences in clinical or cognitive features were observed across variants.
• Twenty-eight participants were in the primary prevention range (EYO: -11 to -35 years) and thirty-three in the secondary prevention range (EYO: -10 to +13 years).

Why it matters

This study characterized 61 people in Colombia with recently identified PSEN1 variants linked to early-onset inherited Alzheimer's disease, most of whom were still cognitively unimpaired. No significant differences in clinical or cognitive features were found across variants, and the authors note that biomarker and follow-up data are still expected.

New to this subject? Start with our plain-English guide: Genetics →

Study details

• Participants61
• Effect size55.7%
• Evidence strengthLow

Read the original

• DOI: 10.1002/alz70861_108984
• PubMed: 41433957
• Original source →
• Free full text: Alzheimer s & Dementia →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

Related studies in Risk genes beyond APOE

• Genetic screening in early-onset Alzheimer's disease identified three novel presenilin mutations Neurobiology of aging · 2019-01-29 · usefulness score 50/100
• Clinical and neuroimaging characterization of Chinese dementia patients with PSEN1 and PSEN2 mutations Dementia and geriatric cognitive disorders · 2014-10-15 · usefulness score 38/100
• SORL1 genetic variants and Alzheimer disease risk: a literature review and meta-analysis of sequencing data Acta neuropathologica · 2019-03-25 · usefulness score 64/100
• Genetic Variants Associated With Alzheimer Disease in the 22 Arab Countries: A Systematic Review Alzheimer disease and associated disorders · 2021-04-01 · usefulness score 50/100
• Identification of PSEN1 and PSEN2 gene mutations and variants in Turkish dementia patients Neurobiology of aging · 2012-04-13 · usefulness score 57/100
• Location of pathogenic variants in PSEN1 impacts progression of cognitive, clinical, and neurodegenerative measures in autosomal-dominant Alzheimer's disease Aging cell · 2023-06-08 · usefulness score 52/100

Also tagged “bodies”

1,017 studies in the library carry the topic tag “bodies”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,017 tagged studies.

• Nucleus basalis of Meynert revisited: anatomy, history and differential involvement in Alzheimer's and Parkinson's disease Acta neuropathologica · 2015-01-30 · usefulness score 53/100 · Lewy body dementia
• Mitochondrial DNA variants observed in Alzheimer disease and Parkinson disease patients Genomics · 1993-07-01 · usefulness score 50/100 · Brain tissue and pathology
• Stable isotope labelling kinetics of neurofilament light Brain Communications · 2025-01-01 · usefulness score 44/100 · Disease mechanisms

Similar studies

• APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases 2017 · Risk genes beyond APOE
• Mutaciones en los genes PSEN1 y PSEN2 como marcadores moleculares en la Enfermedad de Alzheimer. Revisión Sistemática 2025 · Risk genes beyond APOE
• Cuando el Alzheimer llega antes de lo esperado: la mutación del gen PSEN1 2025 · Risk genes beyond APOE
• Biochemical, neuropathological, and neuroimaging characteristics of early-onset Alzheimer's disease due to a novel PSEN1 mutation 2011 · Biomarkers
• Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families 2012 · Brain tissue and pathology
• The genetics of the human APOE polymorphism 2011 · Genetics

More on Risk genes beyond APOE

• A review that covers this ground Presenilin Gene Mutation-associated Psychosis: Phenotypic Characteristics and Clinical Implications Alzheimer disease and associated disorders · 2024-01-17 · usefulness score 50/100
• Newest in this subject Pregnancy History and Loss of Normal PSEN2 Function Impact Female Late-Life Cognitive Processing, Inhibitory Signaling, and Gliosis bioRxiv · 2026-10-30 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject Temporal Proteomics Links the APP London Mutation to Early Cholesterol Remodeling Cell Programs in Human Neurons bioRxiv · 2026-10-24 · Preprint — not yet peer-reviewed · usefulness score 16/100

See all studies in Risk genes beyond APOE →