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Age and Apolipoprotein E*4 Allele Effects on Cerebrospinal Fluid -Amyloid 42 in Adults With Normal Cognition

Elaine R. Peskind, MD; Ge Li, PhD, MD; Jane Shofer, MS; Joseph F. Quinn, MD; Jeffrey A. Kaye, MD; Chris M. Clark, MD; Martin R. Farlow, MD; Charles DeCarli, MD; Murray A. Raskind, MD; Gerard D. Schellenberg, PhD; Virginia M.-Y. Lee, PhD; Douglas R. Galasko, MD

Arch Neurol. 2006;63:936-939.

Background  Decreased cerebrospinal fluid (CSF) -amyloid 42 (A₄₂) concentration, but not A₄₀ concentration, is a biomarker for Alzheimer disease. This A₄₂ concentration decrease in CSF likely reflects precipitation of A₄₂ 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 A₄₂ 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 A₄₂ and A₄₀ 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 A₄₂, but not the A₄₀, concentration decreased significantly with age. There was a sharp decrease in CSF A₄₂ concentration beginning in the sixth decade in subjects with the APOE*4 allele. This age-associated decrease in CSF A₄₂ concentration was significantly and substantially greater in subjects with the APOE*4 allele compared with those without the APOE*4 allele.

Conclusion  These CSF A₄₂ findings are consistent with acceleration by the APOE*4 allele of pathogenic A₄₂ brain deposition starting in later middle age in persons with normal cognition.

Author Affiliations: VA Puget Sound Health Care System, Mental Illness Research, Education, and Clinical Center (Drs Peskind, Li, and Raskind and Ms Shofer), Geriatric Research, Education, and Clinical Center (Dr Schellenberg), and Departments of Psychiatry and Behavioral Sciences (Drs Peskind, Li, and Raskind) and Medicine (Dr Schellenberg), University of Washington School of Medicine, Seattle; Department of Neurology, Oregon Health and Science University (Drs Quinn and Kaye) and Portland VA Medical Center (Dr Quinn), Portland; Department of Neurology, Institute on Aging, University of Pennsylvania, Philadelphia (Drs Clark and Lee); Department of Neurology, Indiana University School of Medicine, Indianapolis (Dr Farlow); Department of Neurology, University of California at Davis, Sacramento (Dr DeCarli); Department of Neurosciences, University of California at San Diego and VA Medical Center, San Diego (Dr Galasko).

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