Background: Decreased cerebrospinal fluid (CSF) β-amyloid 42 (Aβ 42) concentration, but not Aβ 40 concentration, is a biomarker for Alzheimer disease. This Aβ 42 concentration decrease in CSF likely reflects precipitation of Aβ 42 in amyloid plaques in brain parenchyma. This pathogenic plaque deposition begins years before the clinical expression of dementia in Alzheimer disease. Normal aging and the presence of the apolipoprotein E (APOE*4) allele are the most important known risk factors for Alzheimer disease. Objective: To estimate the interactive effects of normal aging and presence of the APOE*4 allele on CSF Aβ 42 concentration in adults with normal cognition across the life span. Design: The CSF was collected in the morning after an overnight fast using Sprotte 24-g atraumatic spinal needles. The CSF Aβ 42 and Aβ 40 concentrations were measured in the 10th milliliter of CSF collected by sandwich enzyme-linked immunosorbent assay. The APOE genotype was determined by a restriction digest method. Subjects: One hundred eighty-four community volunteers with normal cognition aged 21 to 88 years. Results: The CSF Aβ 42, but not the Aβ 40, concentration decreased significantly with age. There was a sharp decrease in CSF Aβ 42 concentration beginning in the sixth decade in subjects with the APOE*4 allele. This age-associated decrease in CSF Aβ 42 concentration was significantly and substantially greater in subjects with theAPOE*4 allele compared with those without the APOE*4 allele. Conclusion: These CSF Aβ 42 findings are consistent with acceleration by the APOE*4 allele of pathogenic Aβ 42 brain deposition starting in later middle age in persons with normal cognition.
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