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

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

doi:10.1001/archneur.63.7.936

Cited by 131Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCerebrospinal fluid and hydrocephalus

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

Peskind, Elaine R., Li, Ge, Shofer, Jane, Quinn, Joseph F., Kaye, Jeffrey A., Clark, Chris M., Farlow, Martin R., DeCarli, Charles +4 more·2006·Archives of Neurology

DOI 10.1001/archneur.63.7.936

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Abstract

BACKGROUND: Decreased cerebrospinal fluid (CSF) beta-amyloid 42 (A beta 42) concentration, but not A beta 40 concentration, is a biomarker for Alzheimer disease. This A beta 42 concentration decrease in CSF likely reflects precipitation of A beta 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 A beta 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 A beta 42 and A beta 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 A beta 42, but not the A beta 40, concentration decreased significantly with age. There was a sharp decrease in CSF A beta 42 concentration beginning in the sixth decade in subjects with the APOE*4 allele. This age-associated decrease in CSF A beta 42 concentration was significantly and substantially greater in subjects with the APOE*4 allele compared with those without the APOE*4 allele. CONCLUSION: These CSF A beta 42 findings are consistent with acceleration by the APOE*4 allele of pathogenic A beta 42 brain deposition starting in later middle age in persons with normal cognition.

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Normal age-related CSF Aβ levels vary with age; CSF Aβ levels seem to decline during young adulthood, and during late mid-life may slightly increase.
“Studies of non-demented individuals report that while CSF Aβ levels seem to decline during young adulthood, during late mid-life CSF Aβ levels may actually slightly increase [219, 220].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [220]

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P2–134: Age and apolipoprotein E*4 effects on cerebrospinal fluid Aβ42 in cognitively normal adults
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Authors: Peskind, E. R., Li, G., Shofer, J., Quinn, J. F., Kaye, J. A., Clark, C. M., Farlow, M. R., DeCarli, C., Raskind, M. A., Schellenberg, G. D., Lee, V. M.-Y., & Galasko, D. R.
Affiliations: University of Washington (US)
Oregon Health & Science University (US)
University of Pennsylvania (US)
Indiana University – Purdue University Indianapolis (US)
University of California, Davis (US)
University of California San Diego (US)
ORCID: Peskind, Elaine R.
Li, Ge
Quinn, Joseph F.
Kaye, Jeffrey A.
Farlow, Martin R.
DeCarli, Charles
Raskind, Murray A.
Schellenberg, Gerard D.
Lee, Virginia M.-Y.
Galasko, Douglas R.
Venue: Archives of Neurology
Publisher: American Medical Association (AMA)
Published: 2006-07-01
Volume: 63
Issue: 7
Pages: 936
ISSN: 0003-9942 (ISSN-L)
DOI: 10.1001/archneur.63.7.936
OpenAlex: W2104954974
Cited by: 131
References: 20
Citations by year: 2026: 2 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 7 · 2019: 4 · 2018: 2 · 2017: 7 · 2016: 3 · 2015: 5 · 2014: 4 · 2013: 14 · 2012: 17
FWCI: 6.96
Type: journal article
Language: en
Open access: closed
Locations: Archives of Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ag008419-15)
National Institute on Aging (AG 10133, P30AG010133, AG08419, AG 08017, AG23185, AG 05136, P30AG010124, P30AG008017, AG-10124, R01AG023185, P50AG005136)
National Center for Research Resources (M01RR000034)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
Keywords: Aβ40, normal aging, Alzheimer's disease risk, cerebrospinal fluid biomarkers, normal cognition
MeSH terms: Adult, Aged, Aged, 80 and over, Aging, Alleles, Apolipoproteins E, Brain, Cognition, Female, Genotype, Humans, Male, Middle Aged, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, Apolipoprotein E4

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

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