Age and apolipoprotein E*4 allele effects on cerebrospinal fluid beta-amyloid 42 in adults with normal cognition
Peskind ER, Li G, Shofer J, Quinn JF, Kaye JA, Clark CM, Farlow MR, DeCarli C et al.. Archives of neurology, 2006-07-01
Topic: Brain proteins, microglia and lab models
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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APA 7th
Peskind, E. R., Li, G., Shofer, J., Quinn, J. F., Kaye, J. A., Clark, C. M., et al. (2006). Age and apolipoprotein E*4 allele effects on cerebrospinal fluid beta-amyloid 42 in adults with normal cognition. Archives of neurology. https://doi.org/10.1001/archneur.63.7.936
Vancouver
Peskind ER, Li G, Shofer J, Quinn JF, Kaye JA, Clark CM, et al. Age and apolipoprotein E*4 allele effects on cerebrospinal fluid beta-amyloid 42 in adults with normal cognition. Archives of neurology. 2006. doi:10.1001/archneur.63.7.936. PMID: 16831961.
BibTeX
@article{peskind2006-16831961,
author = {Peskind, E. R. and Li, G. and Shofer, J. and Quinn, J. F. and Kaye, J. A. and Clark, C. M. and Farlow, M. R. and DeCarli, C. and others},
title = {{Age and apolipoprotein E*4 allele effects on cerebrospinal fluid beta-amyloid 42 in adults with normal cognition}},
journal = {Archives of neurology},
year = {2006},
doi = {10.1001/archneur.63.7.936},
pmid = {16831961},
url = {https://doi.org/10.1001/archneur.63.7.936}
}
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Key findings
- Results The CSF A beta 42, but not the A beta 40, concentration decreased significantly with age.
- 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.
Why it matters
Among 184 people with normal cognition aged 21 to 88, levels of beta-amyloid 42 in spinal fluid fell with age, with a sharp drop starting in the sixth decade in those carrying the APOE4 allele. This suggests that amyloid plaque deposition in the brain begins years before dementia symptoms appear, and that APOE4 speeds this process.
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Study details
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2006 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 131 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.0 citations a year over 22 year(s) since 2006 |
| Impact for its field and year | 3 / 6 | Cited 6.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 24 other studies in this library |
| Still being cited | 1 / 4 | Cited 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Douglas R Galasko: h-index 123 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16831961) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
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