• F Lopera, A Ardilla, A Martínez, L Madrigal, J C Arango-Viana, C A Lemere, J C Arango-Lasprilla, L Hincapíe, M Arcos-Burgos, J E Ossa, I M Behrens, J Norton, C Lendon, A M Goate, A Ruiz-Linares, M Rosselli, and K S Kosik.
• Department of Neurology, Antioquia University School of Medicine, Medellín, Colombia.
• JAMA. 1997 Mar 12; 277 (10): 793799793-9.

ObjectivesTo 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.DesignClinical 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.SettingCommunity based in Antioquia, Colombia.PatientsA 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 MeasuresAge at onset, neuropsychological profile, neurologic history, and examination.ResultsThe 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.ConclusionsOther 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.

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