Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation

Topic: Genetics and APOE

Objectives To characterize clinical features of a very large pedigree with early-onset Alzheimer disease (AD) in which all affected individuals carry the identical glutamic acid-to-alanine mutation at codon 280 in the presenilin-1 gene. Design Clinical histories were obtained by patient and family interviews and through medical or civil records. Using standard diagnostic criteria, a case series of 128 individuals was identified, of which 6 have definitive (autopsy-proven) early-onset AD, 93 have probable early-onset AD, and 29 have possible early-onset AD. Setting Community based in Antioquia, Colombia. Patients A population-based sample in which all members of 5 extended families (nearly 3000 individuals) were surveyed. Criteria for inclusion required obtaining sufficient information to categorize the individual as affected. Main outcome measures Age at onset, neuropsychological profile, neurologic history, and examination. Results The patients had a mean age at onset of 46.8 years (range, 34-62 years). The average interval until death was 8 years. Headache was noted in affected individuals significantly more frequently than in those not affected. The most frequent presentation was memory loss followed by behavior and personality changes and progressive loss of language ability. In the final stages, gait disturbances, seizures, and myoclonus were frequent. Conclusions Other than the early onset, this clinical phenotype is indistinguishable from sporadic AD except that affected individuals frequently complained of headache preceding and during the disease. Despite the uniform genetic basis for the disease, there was significant variability in the age at onset, suggesting an important role for environmental factors or genetic modifiers in determining the age at onset.

Key findings

• Results The patients had a mean age at onset of 46.8 years (range, 34-62 years).
• Headache was noted in affected individuals significantly more frequently than in those not affected.
• Despite the uniform genetic basis for the disease, there was significant variability in the age at onset, suggesting an important role for environmental factors or genetic modifiers in determining the age at onset.

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

Study details

• Participants128
• Evidence strengthLow

Read the original

• DOI: 10.1001/jama.1997.03540340027028
• PubMed: 9052708
• Original source →

Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.

@article{lopera1997-9052708,
  author  = {Lopera, F. and Ardilla, A. and Martínez, A. and Madrigal, L. and Arango-Viana, J. C. and Lemere, C. A. and Arango-Lasprilla, J. C. and Hincapíe, L. and others},
  title   = {{Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation}},
  journal = {JAMA},
  year    = {1997},
  doi     = {10.1001/jama.1997.03540340027028},
  pmid    = {9052708},
  url     = {https://doi.org/10.1001/jama.1997.03540340027028}
}

Related studies in Digital health tools

• Clinicopathological features of familial Alzheimer's disease associated with the M139V mutation in the presenilin 1 gene. Pedigree but not mutation specific age at onset provides evidence for a further genetic factor Brain : a journal of neurology · 1997-03-01 · usefulness score 44/100
• Traumatic Spinal Cord Injury and Risk of Early and Late Onset Alzheimer's Disease and Related Dementia: Large Longitudinal Study Archives of physical medicine and rehabilitation · 2021-01-27 · usefulness score 69/100
• Machine learning model for predicting Amyloid-β positivity and cognitive status using early-phase 18F-Florbetaben PET and clinical features Scientific Reports · 2025-07-01 · usefulness score 50/100
• Stratifying risk for dementia onset using large-scale electronic health record data: A retrospective cohort study Alzheimer's & dementia : the journal of the Alzheimer's Association · 2020-01-16 · usefulness score 62/100
• The prevalence and incidence of early-onset dementia among adults with autism spectrum disorder Autism research : official journal of the International Society for Autism Research · 2021-08-11 · usefulness score 69/100
• Real‐world prediction of early‐onset dementia by health record data: A multi‐center machine learning study Alzheimer s & Dementia · 2025-11-01 · usefulness score 36/100

Also in Digital health tools

178 studies in the library are filed under Digital health tools with no topic tag they share with another; these are this study's neighbours in a fixed tour of them. The Digital health tools hub.

• Gait in Mild Alzheimer's Disease: Feasibility of Multi-Center Measurement in the Clinic and Home with Body-Worn Sensors: A Pilot Study Journal of Alzheimer's disease : JAD · 2018-01-01 · usefulness score 50/100 · Digital health tools
• Retina Fundus Photograph-Based Artificial Intelligence Algorithms in Medicine: A Systematic Review Ophthalmology and therapy · 2024-06-24 · usefulness score 65/100 · Digital health tools
• Clinician Perspectives on Automated Facial Analysis for Pain Assessment: A Cross-Sectional Survey of Physicians, Advanced Practice Providers, and Nurses medRxiv (preprint) · 2026-09-23 · usefulness score 16/100 · Digital health tools

Similar studies

• Familial Alzheimer's disease sustained by presenilin 2 mutations: systematic review of literature and genotype-phenotype correlation 2014 · Risk genes beyond APOE
• Discovery and validation of dominantly inherited Alzheimer's disease mutations in populations from Latin America 2022 · Risk genes beyond APOE
• Early-onset familial Alzheimer's disease (EOFAD) 2012 · Risk genes beyond APOE
• Identification of PSEN2 mutation p.N141I in Argentine pedigrees with early-onset familial Alzheimer's disease 2015 · Risk genes beyond APOE
• Progressive cognitive impairment and familial spastic paraparesis due to PRESENILIN 1 mutation: anatomoclinical characterization 2022 · Risk genes beyond APOE
• Very early onset AD with a de novo mutation in the presenilin 1 gene (Met 233 Leu) 2003 · Risk genes beyond APOE

More on Digital health tools

• A review that covers this ground Clinical, neuroimaging, and pathologic features of progressive nonfluent aphasia Annals of neurology · 1996-02-01 · usefulness score 59/100
• Newest in this subject Speaker-Wise Dementia Screening fromNaturalistic Speech with Lexical Entropy, Semantic Drift, and Multimodal Fusion Research Square · 2026-10-21 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject Integrating Multisource Target Evidence with Machine-Learning Potency Prediction for Alzheimer’s Disease Drug Discovery bioRxiv · 2026-10-20 · Preprint — not yet peer-reviewed · usefulness score 16/100

See all studies in Digital health tools →