Cerebrospinal fluid levels of amyloid β‐protein in alzheimer's disease: Inverse correlation with severity of dementia and effect of apolipoprotein e genotype
Abstract
Alzheimer's disease (AD) is characterized by formation in brain of neurofibrillary tangles and of amyloid deposits. The major protein component of the former is tau, while the latter are composed of amyloid beta-peptides (A beta), which are derived by proteolytic cleavage of the amyloid beta-protein precursor (APP). Both tau and various secretory APP derivatives including A beta and APPS are present in human cerebrospinal fluid (CSF). To investigate whether clinical signs of AD are paralleled by changes in CSF levels of these proteins, we correlated quantitative measures of dementia severity with CSF concentrations of A beta, of APPS, and of tau. We found that levels of A beta in CSF of AD patients were inversely correlated both to cognitive and to functional measures of dementia severity. In contrast, levels of APPS and of tau did not correlate with dementia severity. Apolipoprotein E (apoE) genotype did not influence CSF levels of A beta, APPS, or tau, which were similar among AD patients with Apo E epsilon 3/3, epsilon 3/4, and epsilon 4/4 alleles. These data indicate that CSF levels of A beta decrease with advancing severity of dementia in AD and suggest that they are independent of a patient's Apo E genotype.
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It is well established that Aβ42 declines in the CSF of patients with typical late onset AD.
“It is well established that A42 declines in the CSF of patients with typical late onset AD (Motter et al., 1995;Nitsch et al., 1995;Kanai et al., 1998;Andreasen et al., 1999)”
From Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease (2001) · cites this paper as Nitsch et al., 1995
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Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
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Self-citationAmyloid β-peptide is produced by cultured cells during normal metabolism
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Self-citationProduction of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing
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- Authors
- Nitsch, R. M., Rebeck, G. W., Deng, M., Richardson, U. I., Tennis, M., Schenk, D. B., Vigo‐Pelfrey, C., Lieberburg, I., Wurtman, R. J., Hyman, B. T., & Growdon, J. H.
- Affiliations
- Massachusetts General Hospital (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Nitsch, Roger M.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 1995-04
- Volume
- 37
- Issue
- 4
- Pages
- 512-518
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2163652052
- Cited by
- 113
- References
- 5
- Citations by year
- 2025: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2017: 2 · 2015: 1 · 2013: 1 · 2012: 1
- FWCI
- 7.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (2P50 AG-01534)
- National Institute of Mental Health (NIMH 28783)
- National Center for Research Resources (RR 01066, M01RR001066)
- 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
- Alzheimer's disease, amyloid-beta, cerebrospinal fluid biomarkers, dementia severity, APOE genotype, tau protein, cognitive impairment
- MeSH terms
- Aged, Alzheimer Disease, Apolipoproteins E, Female, Genotype, Humans, Male, Middle Aged, Severity of Illness Index, Amyloid beta-Peptides
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